Noting that hypertension is said to be an extremely rare complicatio n of contraceptive pill use, the author reports this case of a 19-year-old girl given Orthonovin (norethisterone 2 mg and mestranol .1 mg). Her weight rose from 66.6 kg to 71.2 kg and her blood pressure from 115/70 to 200/100 mm of mercury in 2 years. She was changed to Norinyl-1 (norethisterone 1 mg and mestranol .05 mg) and her wieght fell to 66.6 kg and her blood pressure to 130/80. Chlorothiazide and Slow-K were given for 6 days only because of side-effects. She now takes Minovlar (norethisterone 1 mg and ethinyl estradiol .05 mg). Her weight is 66.6 kg and her blood pressure 130/75. A similar case has also been treated at Guy's Hospital. The condition may be more common than hitherto expected.
A suction-curet apparatus for endometrial biopsy.
A suction-curet apparatus for endometrial biopsy is described. The primary application of the apparatus is in the determination of ovulation in cases of infertility. An electric motor suction apparatus is employed instead of suction by syringe. The curved tube cannula is preferred to the straight instrument, and can usually be inserted without dilation of the cervix. The method can also be used for diagnosis of adenocarcinoma of the uterus, hyperplasia of the endometrium, the study of indocrinopathic amenorrhea, and for obtaining fertilized ovum at very early stages of implantation.
Statistics are presented for death from abortion during the 1st half of this century. Abortion is defined as the termination of intrauterine pregnancy prior to the 28th week regardless of cause. Data include changes made over the years in 1) determining primary cause of death; 2) mortality rates; 3) other causes of death from abortion. There has been a steady decrease in mortality from abortion from about 150 to 30 per million reproductive age women. Deaths from septic abortion outnumber deaths from nonseptic abortion deaths. Improved contraceptive methods, more skillful abortionists and better therapeutic drugs account for these changes. Mortality from abortion has been higher among blacks than whites but has declined faster among whites that blacks. Regional differences affect abortion mortality rates, but on the whole the death rate is on the decrease. For comparative purposes, some data is included for Switzerland, Germany, and England.
The chemical profile of dimethisterone is presented. Dimethisterone (6alpha, 21-dimethylethisterone. 6 alpha, 21-dimethyl-17alpha-ethynyltestosterone. 17beta-hydroxy-6alpha-methyl-1 7-(1-propynyl)-androst-4-en-3-one) is a white crystalline powder that is soluble in ethanol, chloroform, and acetone, but not in water. The hydrated form of the drug melts at 103-113 degrees, while the anhydrous form melts at 137-139 degrees. The ultraviolet spectrum of dimethisterone in methanol shows a maximum at 242 mmc. A colorimetric assay has been developed on the basis of the reaction of dimethisterone with sulfuric acid to form a chromogenic substance absorbing at 490 mmc.
Endometrial leukocytes in patients using intrauterine contraceptive devices.
Leukocyte infiltration of the endometrium was studied in women wearing a stainless steel ring intrauterine device (IUD). Adequate specimens from endometrial washings were obtained from 36 women wearing the IUD and 11 control subjects. The mean leukocyte count in IUD-patients was 40, compared to 14 in control subjects (p=.01). Counts under 20 were found in 3 of the IUD-patients (8.3%) and in 10 of the con trol subjects (90%). The differences were independent of the phase of the cycle. The observed inflammation is not the classical endometriosis, and is most likely harmless. The results suggest that the IUD exerts its contraceptive effect by creating an intrauterine environment that is toxic to sperm or the ova.
Some psychiatric aspects of birth control.
As it is the right of every couple to control their family size, physicians and psychiatrists need to be involved in the process of finding an efficient, simple and acceptable means of contraception and making it available to patients as a "mental hygiene measure." 400 married women, 253 Roman Catholics, 112 Jews, 30 Protestants, 5 Greek Orthodox, ranging in age from 16 to 50, the majority supported by welfare, and seeking contraceptive help at a birth control center in New York were studied. Each patient was personally interviewed and a diaphragm was prescribed. Patients were followed for a period varying from 6 months to 3 years at 6 month intervals. The method proved 100% successful in that any failure reported was due to a lack of cooperation by 1 of the partners. Only 10 husbands objected to the diaphragm. Women who had consistently experienced orgasm reported themselves as happier since using the diaphragm. Of the 400 women improved contraception was responsible for a return of or improvement in orgasms in 28% ofthe cases with the general effect of better health and mood and a more positive outlook towards life. Even without a return of orgasm, the women described themselves as more comfortable and content now that the fear of unwanted pregnancy was removed. The use of the diaphragm clearly eliminates worry and tension and consequently the relationship between husband and wife benefits as does the home atmosphere for the children. Birth control is an important addition to a psychiatrist's tools, for it relieves anxiety so that energy otherwise wasted may be used in psychotherapy. Psychiatrists should become involved in the further study of birth control for as a "mental hygiene measure" it is 1 of the most positive. (AUTHOR'S MODIFIED)
On design for experiment and research in fertility control.
A comprehensive and intensive design for experiment and research in fertility control is proposed. The design of the research is based on the assumption that fertility behavior is basically dependent upon the social milieu and that changes in fertility behavior necessarily involve social change. Consequently, changes in fertility behavior cannot be ac hieved by efforts to change attitudes, values, or motivation except in the context of changes in the social order. The proposal involves the following 5 key elements: 1) a fertility control program set up in accordance with the principles of experimental design; 2) a sampling scheme which proposes that a national probability sample be obtained of the study area; 3) the definition of the dependent variable proposes that the dependent variable be the birthrate, general and age specific, and if possible a conception rate along with a measure of the use of various methods of contraception; 4) "control independent variables"; and 5) "experimental independent variables." The results of the experiment would indicate the way in which contraceptive behavior was in fluenced by the varying "dosages" which considered cultural simultaneously with personal and sociological factors. The experiment would provide action programs with information on the most efficient way to bring about fertility control, with maximum result per unit of cost as measured by time, money, and human effort. The general design of the experiment is a broad outline of a major project requiring about 10 years of intensive effort. If this is not possible, the proposal is divisible into a number of parts, but the total design is not necessarily impossible nor impractical. Governments already coping with the fertility control problem could develop an experiment of the type proposed without much expenditure beyond their current effort. A comprehensive experimental program has greater potential of yielding significant results than the current unintegrated, uncoordinated, and non-additive action and research programs.
Medicine and world population.
In interpreting population growth in developed countries, the best answer can be achieved by determining the relative importance of birth and death rates and by accounting for significant factors of the behavior of the 2 rates. Examining 3 periods, before 1770, from 1770-1838, and after 1838 in England and Wales, reveals that in the 1st period birth and death rates were high, in the 2nd period mortality declined, and in the 3rd period, with national statistics available for confirmation for the 1st time, births exceeded deaths. This latter situation has continued until the present. The birthrate remained high until it began a decrease in about 1870. Mortality remained fairly constant until it began a decrease in about 1880. This decline in mortality appears to explain the initial population increase in the late 18th century and the continued population increase after 1870 despite a declining birthrate. The reasons for the decrease in mortality from the 5 diseases or groups of diseases (tuberculosis; typhus, typhoid, and continued fever; scarlet fever; cholera, dysentery and diarrhea; and smallpox) after 1838 were a rising standard of living, changes in the hygiene standards, and a positive trend in the relationship between the infectious agent and the human host. Therapy only had a minor effect on decreasing mortality. It can be said that the progress in the health field since the 18th century has been caused by a rising standard of living from about 1770, sanitary measures from about 1878, and treatment from about 1925. Now that there is an interpretation for the population increase in developed countries, it becomes necessary to deal with the present-day problem of controlling this increase. It appears that this problem can best be resolved by spending time and effort in the native villages bringing about a recognition of the need to limit family size.
Statistical evaluation of contraceptive methods: use-effectiveness and extended use-effectiveness.
Use-effectiveness relates to the experience of a human population with contraception while exposed to the risk of unintended pregnancy. In 1959 a new term, extended use-effectiveness, was applied to the evaluation of the experience of couples who had adopted contraception and had remained exposed to the risk of unintended pregnancy whether or not they continued their contraceptive practice. In studies of use-effectiveness, pregnancy rates tend to decline with duration of use. In studies of extended use-effectiveness, pregnancy rates can be expected to increase for a time as couples abandon contraception and then to decline gradually. A study was done in which each woman was classified by: 1) use effectiveness of all contraception, 2) use-effectiveness of 1st method, 3) extended use-effectiveness of all contraception, and 4) extended use-effectiveness of 1st method. 12 examples of contraceptive experience and a follow-up record are given. By such a study, a coherent framework for evaluation the use-effectiveness, in both senses, contraception as well as continuation is provided.
Population: more than family planning.
Family planning programs often have the limited objectives of promoting voluntary control to attain a desired number of children. It is unlikely that such programs will be able to achieve fertility control or population control, let alone its own limited objectives. If fertility control is to be achieved, family planning programs must recognize abortion as supplementary to contraception; must have as an objective inducing couples to desire replacement levels of fertility; and may have to consider abandoning voluntarism in favor of sanctions and incentives. Although family planning programs should be expanded, they should also be evaluated, and a determination made if other approaches to fertility reduction should be tried. Comprehensive population policies and programs need to be developed which take into account various aspects of population dynamics. (AUTHOR'S MODIFIED)
[Experiences in intrauterine contraception with the DANA SuperIUD]
Clinical experience with the DANA Super IUD in 172 women for at leas t 6 months (2751 use-months observed) is described. Indications include d recent induced or spontaneous abortion, and contraindications or intolerance of hormonal contraception. Insertion, performed on an outpatient basis, is best done immediately before or after the 2nd menstruation after abortion. Spotting occurred in 2/3 of the patients during the first few days after insertion; later side effects included endometritis, adnexitis, pelvic pain, breakthrough bleeding, and hypermenorrhea. The device was removed in 3 cases, and expelled in 6 others. 2 pregnancies occurred in spite of the IUD. The DANA Super IUD is highly effective, has a low rate of side effects, and is very economical.(AUTHOR'S, MODIFIED)
Fertility and economic behavior of families in the Philippines.
Socioeconomic influences on fertility and the interrelated effects of parents' fertility behavior upon their economic activity and welfare in the Philippines are analyzed in order to derive a formula for predicting direct and indirect consequences of various population policies upon fertility levels thereby assuring a more accurate cost-eff ectiveness measurement of a particular policy. A model, which utilizes variables generated from the National Demographic Survey of the Philippines conducted in May 1968, is employed to interpret available data in 5 areas of family activity: marriage, fertility, labor force participation, income, and migration. Primary emphasis is placed on the investigation of fertility determinants. A linear structure of equations representing fertility-related decisions on the timing of marriage, the number of years married, family size, and the use of birth control measures are analyzed by use of statistical methods appropriate to the model. The age at marriage is significantly influenced by the degree of schooling of the woman and her participation in the labor force prior to marriage. The actual decision concerning the timing of marriage is very important because the length of marriage variable deter mines the total number of births for families in all age groups. The use of any birth control method, including the more effective ones, was unpelated to longer open birth intervals. However, knowledge of birth control may be linked with a more rapid birthrate in the younger ages. The interactions between family fertility behavior and labor force participation and income of the women and their husbands are next explored. The significance of recent rural to urban migration patterns is also briefly examined. A concluding section on the policy implications of research findings emphasizes that knowledge of birth control methods is much more widespread than their use.
Studies on male infertility: 6. Clinical observation on male infertility.
Results of clinical observations of male infertility cases seen in S eoul, Korea, National University's Department of Urology between January 1955 and December 1969 are presented. 920 infertile men were seen, repr esenting 3.2% of 36,071 urological outpatients, and 3.9% of 30,125 male outpatients seen during this 15-year period. The number of male inferti lity cases has increased from 10 (1.09%) cases in 1955 to 166 (18.04%) cases in 1969. Primary sterility was found in 78% of the 920 infertile cases in 1969. Primary sterility was found in 22%. The ages of the infertile men ranged from 24 to 61 years (mean=35); the ages of their sp ouses ranged from 24 to 49 years (mean=32). Infertile marital life ranged from 1 to 40 years (mean=7). The duration of infertility cases seen between 1955 and 1959 was 10 years, between 1960 and 1964, 8 years; and between 1965 and 1969, 6 years. There was no close correlation between incidence of infertility and occupation (290 cases were white-collar workers and 414 were physical laborers). Etiological classifications indicate that 40% of the male infertility cases were due to faulty spermatogenesis, 21% due to faulty transportation, 14% due to faulty seminal composition, .5% due to faulty ejaculation, and 24% from unknown causes. In 840 cases where semen was analyzed, 51% had azoospermia, 34% had oligospermia, and 7% had normospermia. In 41 cases analysis revealed normal semen, however, no children have been conceived in 3 years. Testicular biopsies of azoospermias revealed 30% hypospermatogenesis, 27% germinal aplasia, 20% germinal cell arrest, 11% efferent duct occlusion, 9% peritubular fibrosis, and 3% normospermatogenesis. There was no significant difference in average frequency of sexual intercourse between fertile and infertile couples. Medical treatment combined with various drugs (e.g., testosterone, vitamedine) for 3-12 months was most effective in oligospermia (52 out of 101 cases) and azoospermia (13 out of 126 cases). In 22 cases of bilateral epididymal obstruction treated by epidiymovasostomy, viable sperm appeared in the ejaculates of 9. Vasovasostomy performed on 85 previously vasectomized men yielded successful results in 62 of 71 azoospermia cases in which the semen could be repeatedly examined. (AUTHOR'S MODIFIED)
3-month-old female hamsters were checked during the 2 weeks prior to experimentation for vaginal cyclicity. Those showing 3 consecutive cycles were implanted with a 450 micron diameter ball of progesterone or cholesterol on the tip of a 30 gauge needle. Ether was used as anesthesia and implantation was performed between 40-64 hours after ovulation. All implants were midline. The animals were divided into 2 groups; 1 group was ovariectomized on the next expected day of ovulation and the other was checked for vaginal cycles during the 4 weeks postimplantation. Ovulation was checked by counting tubal ova after ovariectomy. Progesterone implants in the preoptic-anterior hypothalamus, just below and slightly posterior to the anterior commissure and above the suprachiasmatic nucleus (frontal sections) suppress ovulation. Implants in the arcuate, ventromedian, or mammillary nuclei did not suppress ovulation. However, progesterone implants in the mammillary region did affect the period of the estrous cycle; it was not uncommon to observe 5 or 6 days between ovulations based on vaginal cytology. Cholesterol did not suppress ovulation when implanted in the preotpic, anterior hypothalamic, suprachiasmatic, ventromedian, arcuate, or mammillary regions. The same size implants do not disturb ovulation or estrous cycles when placed subcutaneously. To have an effect subcutaneously a 2-mm ball of progesterone must be used. Since progesterone is normally present in the hamster and subcutaneous injection of 25 mcg of progesterone inhibits ovulation (American Zoologist 8: 753, 1968), it is proposed that the preoptic-anterior hypothalamus is important as a negative feedback center for control of ovulation by progesterone.(FULL TEXT)
The physical and chemical properties of a crystalline material, derived from corpus luteum extract and possessing progestin activity, were analyzed. Compound A, the main constituent of the mixture, is composed of C21 H34 02, melts at 128 degrees, and is physiologically inactive. Compound B is composed of C21 H30 02, melts at 128 degrees, and has the characteristic physiological properties of progestin. Doses of .5-1 mg Compound B cause progestational proliferation in the castrated rabbit. Its potency is tentatively designated as 1 rabbit unit/mg. Compound C is also physiologically active, melts at 120-121 degrees, and is considered an isomorphic modification of Compound B. It is suggested that the name progestin be retained for Compound B because of its physiological action.
The effect of progestin and progesterone on ovulation in the rabbit.
The ability of exogenous progestin derived from the corpora lutea of sows or progesterone to inhibit ovulation was studied in the rabbit. The animals received either 3 rabbit units of progestin or 1-5 mg of progesterone after which attempts at mating were made, most of which were unsuccessful. In those animals in which mating was achieved there was no indication of ovulation in any of the animals 18 hours after mating. The administration of a minimal ovulating dose of pregnancy urine extract immediately after the refusal of mating resulted in ovulation in 7 of 9 animals. It was concluded that progestin inhibits ovulation by interfering with the postcoital release of pituitary gonado tropin hormone.
The size of uterine cavities was measured by using the planimeter-hysterogram technique. Factors affecting this size were considered. The measured size of uterine cavities was correlated with the occurrence of side effects from subsequent insertion of Lippes loops. Subjects were 45 normal multiparous women. Hysterograms were done with Diagunal as the contrast medium. Visualization of the cervical canal was obtained by using a short-tipped Jarcho's uterine cannula to inject the dye. This device also prevented leakage of the dye into the vagina. The procedure was carried out under fluoroscopy, followed by 3 films in the anterior-posterior position. A film with the cannula in place served to determine measurements. The uterine cavity was considered as a plane since the anterior and posterior walls were almost in contact. A compensatory polar planimeter was used for measurements. Of the 45 women, 32 (71%) had uterine areas between 6-8 square cm. Neither age of patients nor parity was correlated with the size of the uterine cavity. The surface area of the individual, calculated from height, and weight with the Dubois chart had no influence on the size of the uterine cavity. The distance between the fundus and the uterine os varied from 2.9 to 6.4 cm, with most 4-6 cm. The distance between the 2 cornua was 2-3.1 cm. The width of the Lippes loops inserted after the tests was 27.5 mm. 30 of the 45 women had the distance between the cornua less than 27.5 mm. The Lippes loops were 25 mm long. All the subjects had uterine cavities longer than 25 mm. Follow-up studies for 2 years revealed that 60% of the patients had vaginal bleeding immediately after insertion of the Lippes loops and 40% had inc reased bleeding with subsequent menstrual periods. In these 40%, the ut erine area was 6 square cm or less in 55.5% of them. Of those with no s uch complaints only 3.7% had uterine areas of less than 6 square cm. In 30%, pain had followed the Lippes loop insertion. Of these, 60% had uterine cavity areas of 6 square cm or less. In those not having pain only 10% had measurements of 6 square cm or less. Removals of IUDs were made in 40% of these women because of these symptoms. Pregnancy occurred in 12 women within 1 year after removal of the IUDs. There were no expulsions. It is suggested that the frequency of vaginal bleeding and pain is related to the disparity between the size of the uterine cavity and that of the IUD, particularly the width of Lippes loops at present commonly in use (27.5 mm). Newer devices should reduce this width but could increase the length. Fewer side effects and greater acceptability would thereby be promoted.
Fertility after removal of the intrauterine ring.
In order to answer questions most often asked by women using or considering use of the (IUR) intrauterine ring, 305 women who had requested removal of an IUR in order to become pregnant were followed for 18 months. 32.1% of these women conceived in the 1st month after removal; after 18 months, 93.1% had conceived. This figure is comparable to the results of a study by the World Health Organization. The failure of 6.9% of the sample to conceive cannot be attributed definitively to the IUR, as many of these women may have conceived after the follow-up period, and cases of sterility may have resulted from factors unrelated to the IUR. Younger women (mean age = 23.8 years) conceived sooner after removal than older women (mean age = 37.3 years). However, this difference was significant only after 18 months, and conception rates decrease with increasing age in women with no history of IUR use. Because the postremoval fertility rate was much higher for women who had worn the device for 1-18 months than for those who had worn it for 19-36 months, the IUR should be left in place for 2 years, removed for 1-2 months, and then reinserted if continued contraception is desired. The IUR may postpone conception, but it does not cause permanent infertility. Furthermore, in this sample, most women who became pregnant while the IUR was in place had normal labor. The IUR does not seem to cause malformations in pregnancies that occur while the device is in place or in pregnancies after removal.
Metabolic effects of steroid contraceptives.
Literature on the metabolic effects of steroid contraceptive agents is reviewed. Oral contraceptives (OC) do not seem to produce marked changes in tissue levels of carbohydrates. Abnormal glucose tolerance tests have been reported by some investigators, though the greatest changes appear to occur in women with a pre-diabetic condition or a family history of diabetes. The effect of OCs on glucose tolerance seem to be dose-related, and OCs containing mestranol have a greater effect than ethinylestradiol. The pre-diabetic changes induced by OCs are considerably milder than those occurring during pregnancy. OCs have frequently been found to produce considerable effects on the major lipid constituents of blood. It seems likely that all high-dose OCs produce increase in serum non-estrified fatty acids, triglycerides, phospholipids, cholesterol, and lipoproteins. In some women, it appears that changes in blood lipids are spontaneously reversed after 6-12 months. Lipid changes may be involved in weight gain in OC users, though there is no evidence that such changes contribute to a tendency to atherosclerosis. It appears that the degree of lipid changes are proportional to the estrogenicity of the compound taken. The decrease in plasma alpha-amino nitrogen during OC use probably indicates an equilibrium shift in proteins and circulating amino acids, which may be due to an increase in tissue mass and weight gain. OCs also cause an increase in the catabolism of tryptophan, and it is suggested that abnormal tryptophan metabolism is associated with emotional depression. Abnormal tryptophan metabolism, induced by OCs, may aggravate rheumatoid arthritis. OCs increase blood circulating factors VII, IX, X and fibrinogen, though low-dose progestogen preparations do not seem to affect the blood clotting mechanism. It is not yet possible to establish a clinical correlation between particular blood clotting factors and the incidence of thromboembolism. Little change in hemoglobin levels occurs among OC users, though serum iron and iron-binding capacity are considerably increased. The blood plasma of many OC users is normocalcaemic, but also hypophosphataemic and hypomagnesaemic, the latter leading to muscular convulsions over the long-term. Low plasma magnesium levels also enhance blood clotting. Most combined and sequential OCs suppress the release of luteinizing hor mone, but have little effect on other pituitary trophic hormones. Acne and hirsutism may be diminished by the decrease in androgen excretion among women taking OCs. Estrogens increase the level of plasma corticosteriod-binding globulins, thus increasing plasma blood cortisol. Most OCs reduce or eliminate the mid-cycle peak of urinary pregnanediol and reduce estrogen excretion. OCs reportedly increase levels of insulin and growth hormone. Estrogen-dependent effects of OCs on thyroxine-binding globulin produce alterations in thyroid function tests. Estrogen also seem to be responsible for changes in BSP retention, thymal turgidity, and, occasionally, serum alkaline phosphatase and transaminase. Severe cases of jaundice, though rare, have been reported for OC users. OC use must be discontinued in cases of liver infection.
[Contraceptive advice for the young]
Contraceptive counseling of youth is part of sex education in the br oadest sense. Because of the acceleration of physical development and changing sociological situations, the physician is increasingly confront ed with the problem. He is a witness of the process of development and must place himself helpfully at the disposal of his patients. The techniques of contraception, therefore, form only part of the physician's advice. Counseling the young must be done with special care to avoid damage. It is the physician's duty to provide contraceptive advice and counseling to young and unmarried individuals who seek it.(AUTHORS', MODIFIED)
Basic science and human reproduction.
There have been recent developments in 3 areas of biomedical research in the field of fertility control. The knowledge of cellular science has been applied to studies on the ovary and the ovum. Much has to be done to identify the controlling factors initiating the synthesis of RNA in the oocyte. Such knowledge is essential to controlling the ovarian process. There is still much to learn about the action of LH in triggering ovulation. Collagenase is being studied as a possible suppressant to RNA, and thus a suppressant to ovualtion. Cellular research is also investigating capacitation of spermatozoa and the mechanism by which the spermatozoa actually fertilizes the ovum. A recent advance, allowing further study of capacitation and fertilization has been the development of a procedure to fertilize mammalian eggs in v itro. A 2nd area of research has been in early embryonic development and in the passage of embryos from the oviduct into the uterus. Estrogens, anti-estrogens, and diphenylindenes are known substances which may interfere with ovum transport or implantation. Suppression of the release of LH may in turn affect estrogen levels and thus suppress implantation. A 3rd area of biomedical research is in developing a male contraceptive which would block spermatogenesis. Experiments have been conducted with alpha-chlorohydrin which may prove to be an alkylating agent. High doses of various hormones, such as estrogens and androgens will also suppress spermatogenesis, probably by suppressing LH and thereby reducing the endocrine support for spermatogenesis. It is hoped that an artificial androgen could be developed which would suppress LH, but maintain libido.
Rhythm: a hazardous contraceptive method.
The acceptance, applicability, use-effectiveness, and future practicality of the rhythm method of birth control was assessed in 10 family planning centers in Colombia. The acceptance rate ranged from 0% to 40%, for an average of 14.1%. The percentage of women using the rhythm method dropped from 21% to 8.8%, while acceptance of the intrauterine device rose from 8.4% to 27.5% of all methods used. The use of the basal body temperature chart was extremely difficult to teach, and husbands were often uncooperative in abstaining during the fertile period. Follow-up efforts were considerably more expensive for the rhythm method than for other methods. The lowest failure rate for the method among the centers was 36.2%. It is concluded that it is virtually impossible, if not hazardous, to implement a mass family planning program based on the rhythm method.
Irregular menses -- overripeness and fetal anomalies.
The possible association of irregular menstrual periods and overripeness of the ovum with fetal anomalies is discussed. Fetal anomalies occur most frequently among women who are 15 years of age and those who are over 35. It has been reported that the possibility of a normal conceptus decreases from 92% to 42% if ovulation occurs on Day 15, or later, of the cycle. Suppression of luteinizing hormone release for 48 hours in rats resulted in normal ovulatory rates, a decreased fertilization rate, increased embryonic anomalies, and a reduction in th e number of implantation sites. Embryonic abnormalities in aged rats increased with an increase in the frequency of irregular cycles. The similarities in the conditions associated with fetal anomalies between rats and humans should not be disregarded.
Sperm motility and survival in relation to glucose concentration: an in vitro study.
The effect of glucose on human sperm motility and viability was studied in vitro. At low concentrations of glucose, sperm motility was markedly depressed, but increased proportionately with increased glucose concentrations, reaching a plateau at 20-30 mg/ml of glucose in buffered solution. The results support the proposition that cervical mucus must contain at least 200 mg/100 ml of glucose during the fertile period. A hostile cervical environment may reflect a deficiency in glucose content in cervical mucus.
[Activity of the pregnancy interruption commissions in Berlin]
The channels through which an application for interruption of pregna ncy passes are briefly described. After pregnancy is diagnosed, the application is reviewed by 2 experts, usually gynecologists, who must make their recommendations with a view to the patient's present and future health status. The uniform judgement of the indications for an interruption of pregnancy has not yet been achieved in Berlin: the percentage of applications approved varied between 52.3% and 83% in various districts of the city in 1968. (For Berlin generally, 1508 of 2073 applications were approved, or 75.7%.) The author recommends that members of the commissions avail themselves of all therapeutic possibilities to encourage the applicant to bear the child.(AUTHOR'S, MODIFIED)
The effect of medroxyprogesterone acetate upon the duration and char acteristics of human gestation and labor was studied. 200 pregnant women (36-38 weeks gestation) were randomly assigned to a group receiving 20 mg 4 times/day or to a group receiving only the tablet base. This double-blind study failed to reveal any effect upon the duration of pregnancy or the characteristics of pregnancy, labor or fetal conditions.
Oral contraceptives and thromboembolism.
Reports quoted confirm previous investigations regarding the association between the use of oral contraceptives and deep-vein thrombosis and pulmonary embolism. 1 study showed that the use of oral contraceptives increased the risk of thrombosis 3 times; another study showed that 38% of women with venous thrombosis who were admitted to a hospital had been taking oral contraceptives while only 8% of controls had been using these drugs. An investigation by the Committee on Safety of Drugs suggested a relationship between oral contraceptives and death from pulmonary embolism. Such deaths were estimated to occur in 3 of every 100,000 users per year. Findings suggest it is the estrogen which is responsible; sequential types may, therefore, be more dangerous as they contain more estrogen. Chlomadinone acetate used without estrogens may be safer. Use of estrogens for other than contraceptive purposes, particularly if given in high dosage or for long periods, may also carry a risk. Thromboembolic disease in 1 of ever 2000 women per year of those taking oral contraceptives has been estimated and requires more attention.
Family planning programme in Punjab.
Since the reorganization of the state of Punjab, India, in 1966, the government has undertaken an aggressive program of family planning, conc entrating on the promotion of both male and female sterilization and IUD insertion. It is estimated that by 1967 about 50% of the eligible couples were using some form of contraceptive. 2 intensive campaigns in 1966 and 1967, for 37 and 45 days, respectively, were launched to enlist people in birth control programs. Approximately 1/2 of the year's IUD insertions and 3/4 of the sterilizations were done during these brief periods. In the period 1961-1967 the national growth rate decreased from 23.13 to 20.88 per thousand. Currently, family planning services in Punjab are available on a "cafeteria" basis, with all contraceptive methods presented to the prospective user so that he can make a personal choice with the aid of medical or paramedical personnel. There are also government sponsored family planning camps for loop insertions, vasectomy, and tubectomy. Leave and financial incentives are provided to persons undergoing sterilization or loop insertion. Charts, graphs, and other illustrative material are included.
Oral contraceptives and gastrointestinal disorders.
4 case histories of gastrointestinal abnormalities which developed in association with the use of oral contraceptives are presented. These were all cases of mesenteric vascular disease, confirmed through operative diagnosis. 2 cases exhibited massive bowel infarction necessitating resectioning.
MINI-TAB: a packaged cross-tabulation program for processing survey data on small computers.
MINI-TAB is a packaged computer program which cross-tabulates and makes charts out of files of data. The program can be used on a variety of electronic computers, even machines with a minimum of core storage. MINI-TAB performs 3 functions: 1) it regroups, recodes, and selects data for charts; 2) it computes frequencies and percentages for cells, rows, and columns; and 3) it calculates statistical associations. To use the program the user merely changes the instruction card in the program. Co des in the program will set up the table with indications for the width of data fields. Control cards indicate horizontal and vertical lines in the table.
Participation in United Nations Interregional Seminar on Demographic Aspects of Manpower.
This report informally describes a seminar on the relation between demography and manpower organized by the Population Division of the United Nations. This United Nations Interregional Seminar on Demographic Aspects of Manpower discussed relationships between population growth and needs in the labor force. Statistical methods for projecting population and manpower figures were discussed. Fertility control programs, a controversial area, were mentioned.
In 1969 the world's population increased by 71,000,000 with only 6.9% of these births in Europe but with 63.4% in Asia. The problems of overpopulation are evident in the extent of malnutrition, pollution, and overcrowded cities throughout the world. Even where family planning projects have been attempted, they have for the most part been unsuccessful because there first must be improvement in education and living standards and the establishment of adequate maternal and child welfare services before family planning can be accepted. In Britain a committee of senior civil servants has been set up to study the problem of population growth. The select committee on science and technology of Parliament appointed a subcommittee on the subject. Hopefully these beginnings will lead to a needed permanent committee on population and the environment.
In a study on fertility control and small families, it was found tha t data were unavailable to test the hypothesis that a feeling that children interfere with personal freedom motivates fertility control and small families. Only among couples who have remained childless does the desire to avoid restriction of personal freedom seem to have been a motivating factor. An alternative hypothesis was proven: Among couples with children, a feeling of restriction develops from the difficulties and hardships experienced. Women seem to feel more restricted by children in all socioeconomic groups than do men. The feeling of restriction increases with unsuccessful fertility, number of children, and low socioeconomic status. Having 3 or more children correlated highly with feelings of personal restriction. It is speculated that the feeling of restriction experienced by couples of high socioeconomic status relates to different values regarding family building and not to economic difficulties. The factors that were experienced (lack of success with family planning, actual number of children, or the objective difficulties related to economics) were less important to the couples' feelings than was the subjective interpretation of the experiences.
[Genetics of fertility and sterility.) (Domestic animals]
Fertility can be affected by genotype, environment, ovum or sperm function, congenital defects of the reproductive system, endocrine function, sexual function, and hereditary predisposition to certain disorders. Genetic traits affecting fertility are generally polygenic, but selection for fertility should be possible in species subject to art ificial insemination. Instead, it is probable that universal artificial insemination (to the extent that some bulls have 50,000-250,000 descendants and the male/female ratio is 1:1000-3000 in cattle) has decreased fertility. Environmental factors affecting fertility include photoperiod, breeding time, physical hygienic and climatic conditions, feeding and stress. Hormonal stess such as oxytocic stress from mechanical milking and adrenal stess from crowding may affect fertility. Hormonal function is selected for in egg-laying hens and probably in dairy cattle. Immunogenetic factors may act at the level of different parts of the male reproductive tract, decapacitation factor, blood group antigens, sex-linked antigens. Maternal-fetal incompatibility may account for 45% of embryonic loss in swine, 30% in c attle. For example, dairy cattle are known to reproduce more successfully if they are homozygous for serum beta-globulins. Morphologic of functional defects, some of which have been characterized as recessive autosomal, have been documented in several strains of cattle. Methods of choosing males for sperm donors must be improved and based on rigorous scientific principles rather than on traditional customs.
Report of Near East/South Asia/Far East workshop on literacy/population/ family planning education.
In order to encourage and implement the use of population/family planning information in literacy programs in the developing world, a workshop was held in India in 1970 with attending personnel from Afghanistan, India, Iran, the Philippines, Thailand, and Turkey. The objectives of the workshop were to share experiences in preparing and using teaching and reading materials; to explore common needs which could serve as a basis for joint planning and resource pooling; to assist in the design and planning of demonstration projects for developing materials and introducing population/family planning information into adult literacy and family planning education programs; and to assist in the identification of the technical assistance and supporting services needed to achieve these objectives. It was felt by the participants that these objectives were met.
A study of environmental factors in carcinoma of the cervix.
Epidermoid cancers rarely occur in sites not exposed to exogenous factors of irritation. To study the role of environmental factors in the production of cervical cancer, a clinical-statistical study was carried out jointly in the United States and India. A review is given of the incidence of cervical cancer as encountered in various population groups including: Jews, Fijis, Moslems, Negroes, low-income groups, marital status groups, and prostitutes. This study was an attempt to determine by personal interview whether factors that could explain variations in the incidence of cervical cancer among the different population groups could also explain variations within each group and vice versa. The major associations which this study suggests or confirms are marital status, age at 1st marriage, age at 1st coitus, number of marriages, and circumcision status of the partner. However, statistical associations do not by themselves necessarily establish the etiological significance of the associated factors. The present results are compatible with the concept that those population groups having a late age at 1st coitus and 1st marriage and low remarriage rate, whose men are circumscribed, have a lower rate of carcinoma of the cervix. Carcinogenesis represents the effect of many factors some of which may be endogenous and some exogenous.
A study on ovulation inhibition by Quinestrol: one dose a month.
The efficacy and safety of Quinestrol in a single-dose-a-month regimen for inhibition of ovulation was studied. 10 women received 2 mg Quinestrol on Day 1 of the first treatment cycle and 2 mg Quinestrol plus 50 mg medroxyprogesterone (Provera) on Day 22. During treatment Cycles 2, 3, and 4, 2 mg Quinestrol plus 50 mg Provera were received on Day 22, and in Cycle 5 no medication was received. Basal body temperature, urinary pregnanediol and urinary follicle-stimulating hormo ne determinations, vaginal cytology, and endometrial biopsies were performed during each cycle. The single 2 mg dose inhibited ovulation in 60% and delayed ovulation in 35% of a series of 40 cycles. The human safety laboratory studies did not reveal any abnormalities, and the side effects were mild in nature. It was concluded that this regimen might prove adequate for more effective inhibition of ovulation with larger do ses of Quinestrol.
Edward Foote's Medical Common Sense: an early American comment on birth control.
The 1864 edition of Edward Foote's Medical Common Sense is remarkabl e because it candidly supported birth control. The hazards of multiple pregnancy to maternal health were mentioned, but Malthusian concerns wer e primary. Folk methods of birth control were denounced. The methods t hat were currently in use--the glans condom, the regular condom, and the cervical diaphragm--were discussed. Because of his unorthodox views, Foote was convicted under the Comstock law in 1876. He continued to advocate birth control up to his death in 1906.
Prevention of pregnancy in the rabbit by the sc implantation of a silastic tube containing estrogen but not by similar implantations containing progesterone or ethinyl estradiol is reported. 10-14 days after implantation rabbits were mated and laparotomies done 2 days after to determine if ovulation had occurred. When ovulation had not taken pl ace, rabbits were artificially inseminated 12-14 days later and also injected iv with 50-90 I.U. of human chorionic gonadotropin (HCG) to induce ovulation. Animals were killed at 2, 6, or 12 days after mating or insemination. At autopsy the silastic tubes were removed and the rate of absorption of the compound calculated. The rates of absorption varied for different animals but were not correlated with day of removal. Tubes containing progesterone or ethinyl estradiol had not prevented ovulation. Ovulation had failed in 3 of 11 rabbits treated with estrogen. The average number of corpora lutea was reduced in those treated uith estrogen; 5.67 plus or minus .74 in 18 estrogen-treated animals, 12.7 plus or minus .64 in 20 treated with progestin, and 10.30 plus or minus .90 in 10 controls. Also the proportion of eggs recovered and of embyros obtained to corpora lutea was less in the estrogen-treated rabbits (28% compared with 90-91% in the other animals). The proportion of eggs fertilized was not affected. Failure of implantation was increased in estrogen-treated rabbits but not in the others. In estrogen-treated rabbits disturbance of egg transport seemed to increase the number of degenerated but fertilized eggs. The use of such procedures for contraception is recommended for further investigation.
An experiment was conducted to determine whether the luteolytic effect of the IUD inserted into the uterine horn contralaterad to the ovary containing the corpus luteum is exerted through systemic channels such as the general circulation of through a direct pathway to the opposite side such as the uterine lumen or the intercornual tissues. IU D was inserted in the uterine horn on Day 1 of the estrous cycle. Early regression of the CL occurred, as indicated by weight of CL on Day 10. Removal of the ipsilateral uterine horn or surgical separation of the 2 uterine horns from each other interfered with the luteolytic action of the IUD located contralaterad to the CL. Suturing the broad ligament from the unilaterally hysterectomized side to the uterine-intact side seemed to restore partially the luteolytic properties of the IUD. Sever ance and ligation of the uterine horn caudad to the IUD apparently did not interfere with the luteolytic action of the IUD, whether the IUD was contralaterad or ipsilaterad to the CL.(AUTHOR'S, MODIFIED)
The work of the Contraceptive Testing Centre of the Government of India.
The work carried out by the Contraceptive Testing Unit, a team of In dian Government research workers, is discussed. Colposcopy is described as it is used in detecting changes on the vaginal and cervical mucosa. 2 kinds of contraceptives are investigated by the Unit: oral and local. Biological testing of oral contraceptives is carried out for the Unit, which is chiefly concerned with developing substances capable of preventing fertilization or implantation. In studying local contraceptives, it must be determined whether the contraceptive meets 3 main requirements: effectiveness, harmlessness, and acceptability. For evaluation of these criteria, the local contraceptive studied by the Government Testing Unit must be submitted to laboratory tests, clinical tests, clinical trial, and a field trial. As changes in the cells and cellular architecture of the surface epithelium can be detected by magnified observation with the colposcope, it is possible to note the slightest changes in the cervical and vaginal mucosa, occurring after the "10 minutes test," the "Cap Test," and long-term use of the contraceptive.(AUTHOR'S, MODIFIED)
1 of the main measures taken to create an equilibrium between the natural resources and the expected economic growth and the population gr owth in Egypt was the establishment of family planning clinics. 8 of the clinics were established in 1955. In 1956, there were 12 family planning clinics in Egypt. Assistance is given in the clinics in 1) raising the standard of living through limiting the number of children; 2) spacing the number of children so the mother and children will be healthier; 3) treating sterility cases in order to help the childless family to get children; 4) evaluating the efficiency of the various methods of birth control anc selecting the most suitable methods to be used in various cases; and 5) collecting information about the number of children each family tends to have and the reason for such tendencies. The personnel at the clinic includes a doctor, social worker, and nurse. Suitable drugs and instruments used are given for half their cost price. (AUTHOR'S, MODIFIED)
Discovering the degree of commitment to family planning in a Calcutta City Project.
2 sections of Calcutta, each with about 10,000 residents, were selected to study changing family planning attitudes, behavior, and fertility over a 3-year period beginning in June 1964. 1500 couples from Center 1 were exposed to an action program on family planning; 1500 couples from Center 2 served as a control group. Data were collected at 6-month intervals to measure the impact of the action program. KAP data were collected on a limited sample basis from an extra block as a means of cross-checking data from the original survey and of obtaining data on attitudes, knowledge, practice, and sources of procurement. The data are presented in 20 tables broadly classified as general tables and attitude tables. The general tables are presented by 3 variables: age of husband, age of wife, and education and occupation of husband. The attitude tables are grouped into 4 subcategories: 1) acquaintance with family planning methods by education and occupational level of husband, sources of knowledge of husband and wife; 2) adoption of family planning by education and occupation of husband and by education, occupation, and willingness type of both spouses; 3) nature of steps adopted by education and occupation of husband and sources of procurement, types of methods adopted by education and occupation, and reasons for not adopting steps; and 4) desire for additional children by age of husband and wife and desire for additional children by surviving number of children.
The recent U.S. Senate hearings on oral contraception have engendered statements of opinion from both The American College of Obstetricians and Gynecologists and the Board of Directors of the American Fertility Society. Both have endorsed the Second Report on Oral Contraceptives of the Advisory Committee on Obstetrics and Gynecology to the U.S. Food and Drug Administration (FDA), which gives tacit approval for the continued prescription of oral contraceptives. Confusion regarding oral contraceptive usage stems from the difficulty involved in assessing and interpreting numerous variables. Such evaluation is necessarily influenced by the moral, ethical, social, political, economic, and medical attitudes of the assessor, as well as the user. Inasmuch as we do not have a legal definition of "safety," our actions are modulated by the collective opinions of responsible agencies - in this case the FDA. Presently there is no consensus on what comprises adequate toxicity evaluation of pharmacologic agents in general. The unqualified assumption that observations in the laboratory animal are uniformly applicable to the human is not justified. Furthermore, in interpretation of human data, hereditary and social factors must be considered. It is generally acknowledged that associated serious side effects of contraceptive pill usage occur infrequently. Causal relationships are difficult to establish, but the possibility of such relationships cannot be dismissed summarily. Since these agents are so utterly effective as contraceptives, any potential hazard must be weighed against the medical and social risks of an undesired pregnancy, as well as the risk of daily activity. The public has a right to accurate, unbiased information. Overreaction to some preliminary findings does not serve the best interests of either the public or science. Careful, responsible reporting and interpretation of data within the context of a given study are to be encouraged. There must be continued efforts to establish reasonable guidelines for the use of all pharmacologic agents, including the "pill". Physicians are accepting increasing responsibility for society's needs. Contraception is no exception. It is clear that every effort must be made to make periodic physical examinations, with cytologic studies, available to all. A careful review should always be undertaken to uncover potential contraindications to any contraceptive practice. Such comprehensive care necessarily includes helping the couple in their selection of the contraceptive modality most appropriate to their individual circumstances. Within such limitation, the oral contraceptives are a reliable therapeutic method and may yet prove to be the most valuable contribution to the welfare of society in the past decade. (FULL TEXT)
It has been shown that the X and Y chromosomes associate at meiotic prophase in the human male, but there has been speculation on whether it is the long or the short arm of the Y chromosome which associates with the X. Definitive evidence is presented that the latter takes place during the first meitoic prophase. Diakinetic cells were prepared according to the technique of Evans et al., stained with quinacrine dihydrochloride, and viewed with a Leitz microscope fitted with an HBO 200 light source and a Ploem vertical illuminator. 50 cells were selected from a normal male which showed differential fluoresecence. The X-Y bivalent was examined under ultraviolet light and under phase contrast. It was determined that where the X and Y chromosomes were associated, the more highly fluorescent region (the distal ends of the long arm fluoresce with the quinacrine stain) was at 1 end of the sex bivalent and not in an interstitial position. In cases were the chromosomes were lying free, the Y chromosome had a highly fluorescent a rea and a less fluorescent area which mirrored the staining distribution of the Y chromosome during mitosis. It was concluded that the short arm s, centromere, and proximal parts of the long arm are in the less fluore scent part of the chromosome as they are in the mitotic Y chromosome.
The Y chromosome in human spermatozoa.
Attempts have been made to distinguish between spermatozoa of mammal s containing either an X or a Y chromosome. It has been determined that the distal end of the long arm of the Y chromosome in mitotic and meiotic metaphase nuclei of human cells displays a fluorescence more brilliant than that shown by the other chromosomes when stained with either quinacrine or quinacrine mustard. When human spermatozoa were stained with quinacrine or quinacrine mustard, slides prepared, and viewed uith fluorescent illumination from a Zeiss photomicroscope using exciter filters for transmission ranges between 330 and 500 mn, some sperm showed a fluorescent body (F-body) which was brighter than the bulk of the fluorescent material. It is believed that the F-body represents the Y chromosome because: 1) In mitotic and meiotic metaphases, part of the Y chromosome fluoresces more than any other chromosome as does the F-body; 2) In interphase nuclei of normal XY males there is only 1 strongly fluorescent spot of chromatin, while in nuclei from XYY males there are 2 spots, and the nuclei of normal XX females exhibit no such spots. The frequency with which F-bodies are seen in sperm approaches that expected from the segregation of the Y chromosome at meiosis. It is presumed sperm lacking an F-body lack a Y chromosome and therefore may be X-bearing sperm.
The author reviews the history of the Bermuda Health Department's ef forts to promote population control among the island's black population. Political, social, and moral resistance by the black population to birth control is described, and lines of opposition from other sectors of the population during the initial efforts are reviewed. Social conditions that tend to promote illegitimacy are descr ibed, and legislative efforts (particularly that which required caring for illegitimate children) to reduce the illegitimacy rate are noted. Birthrates and illegitimacy rates are given for the years 1938, 1940, 1950, 1954, and 1955 along with corresponding public events. Public health nurse visits during the early phases of the program resulted in only 50 new patients a year. From 1954-1955 new cases increased from 200 to 650. This latter increase was accompanied by a reduction of births from 27 per 1000 to 25 per 1000 population though illegitimate births increased slightly.
A cheap and harmless oral contraceptive is needed to check world population growth. One substance, m-Xylohydroquinone or 2:6 dimethyl hydroquinone, has proven satisfactory in tests. It has no toxic effects, is not an abortifacient, and does not cause permanent sterility. For rural, illiterate India it is unsatisfactory because this substance must be taken on Days 16 and 21 of the menstrual cycle. Women in these areas cannot count and have no sense of time. A substitute compound has been developed at the Calcutta Bacertiological Institute, 2:6 diethylhydroquinone. This needs administering only after the menstrual period stops. Tests by several international laboratories indicate that this compound is at least a somewhat satisfactory oral contraceptive.
Community education in family planning.
Community education in terms of family planning in the case of India is examined. Having no children or having less than the accepted norm may well be a social stigma; therefore, there may be socal pressure on a woman to not consider the services of a family planning clinic. If the pressure could be made to work positively than the whole trend may reverse itself. The motivational trends should be understood by the family planning worker fully so that suitable methods of health education for family planning may be chosen. A group discussion method may work well in terms of changing attitudes and motivations. Another factor that may help the success of family planning would be providing sex education to children. Community programs of family planning should not only offer services but should also educate the public as to the availability of the services.
Progress and problems of family planning in the United Arab Republic.
The rapid population growth in the United Arab Republic (URA) is bec ause of 1) the large rural population (57%), 2) the agricultural economy , 3) high illiteracy, 4) high infant and child mortality, and 5) the hig h incidence of divorce and polygamy. There are an estimated 2,000,000 women of fertile age with 2-3 children. The goal of the governmental family planning program is to reach 1,000,000 women by 1970, reducing the rate from 2.54% in 1968 to 2.1%. IUDs and oral contraceptives are manufactured within the country. Acceptance of both is low in rural areas. Problems associated with the family planning program in the UAR include inaccuracy of statistics, interagency staff distribution, poor location of new centers, bureaucratic demands, need for more village centers or mobile units to reach rural areas, fixed working hours that are inconvenient for acceptors, lack of social workers, lack of availability of contraceptives, inadequate communication and motivational efforts, lack of sufficient full-time personnel, welfare advantages given to large families, and lack of centralized industries.
Rhythm of sexual desire in women.
Literature on the rhythm of sexual desire in women is reviewed and a preliminary study is presented. A major difficulty in past studies has been the woman's seeming ignorance of her own physiology. Although there is general agreement that peaks of sexual desire do occur, there is little agreement on when they occur. In a study of 30 women, sexual desire was apparently strongest during the postmenstrual and early ovulatory periods. The rhythm method of birth control, therefore is a source of sexual frustration for many women.
Chemical nature of the urinary "pregnancy test" with iodine.
This study evlauated the claim that the addition of iodine to the warmed urine of pregnant women produces a red pigment which is extractable with amyl alcohol and is diagnostic of pregnancy. Under optimal conditions 163 of 168 urine specimens of pregnant patients gave a positive test. However, 86 of 142 random urine samples from nonpregnant women or males also gave positive tests. The red pigment found when pregnancy urine reacts with iodine results from a reaction between uric acid, iodine, and tryptophan; uric acid is oxidized by iodine and the unstable intermediate reacts with tryptophan. Most urines of pregnant women have enough tryptophan to give a positive test. However, a positive test is an indication of hypertryptophanuria and not a specific test for pregnancy.
Motivation for and problems in establishing an evaluation mechanism in the State of West Bengal.
The government of India was presented with a plan by West Bengal, in 1967, to establish an evaluation program of the Family Planning efforts. The main objections of the government to the first plan was its cost and the need for highly qualified personnel. In July 1968 the plan was resubmitted to the government with proper modifications. It was not acted upon favorably. A third proposal was submitted in 1969. Action was being awaited at the time of this article. Problems complicating the development of an evaluation mechanism for West Bengal include the largeness of the country, the need for expertise, and the cost of an evaluation program.
Organization and motivation for evaluation.
One of the main difficulties in implementing an evaluation program of family planning programs is to get it accepted. Organization and motivation become very important in that case. Misunderstandings over the meaning of the term evaluation, the relationship between management and evaluation, and the relationship between internal and external program evaluation present problems with the acceptance of evaluation. The role of the advisor in establishing an evaluation program then is to help alleviate these problems; namely, to help analysts and managers understand the objective, the role, the purpose, etc. of the evaluation program. In order to accomplish this task, the advisor has to have a working knowledge of the program with its strengths and weaknesses, and a knowledge of installing a system for program evaluation.
Total cesarean and puerperal hysterectomy: a report of 205 cases.
A series of 205 total hysterectomies performed at cesarean section or in the puerperal period is reported. Although this total was collected during a 7-year period, 1949-1956, it represents the material from approximately 50,000 deliveries, a section rate of 3.72% of which 45% are repeat procedures. There were no surgical complications in 180 patients, 16 were in shock, there was hemorrhage in 4, afibrinogenemia in 4, and spinal shock in 1. Postoperative complications were observed in 59 patients, most of which were of a mild nature. There was 1 bladder injury, a vesicovaginal fistula which responded to treatment. There were 30 stillbirths, 10 of which occurred in conjunction with rupt ured uteri, 18 from abruptio placentae, 1 from erythroblastosis, and 1 from a neglected transverse lie, a rate of 14.6%. 3 maternal deaths occurred and are considered incidental to the procedure. 1 death followed long-standing peritonitis associated with uterine rupture; 1 patient with eclampsia, abruptio placentae, and lower nephron nephrosis died on Postoperative Day 20 of cerebral thrombosis; the third patient died at home on Postoperative Day 19 of a pulmonary embolus. Operative experience has shown that there is no reason to leave the cervix in situ. It is concluded that whenever hysterectomy at the time of cesarean section or in the puerperium is indicated, a total abdominal hy sterectomy can and should be performed.(AUTHOR'S, MODIFIED)
Inhibitory effects of steroids on gonadotrophin secretion in the male rat.
In assessing the capacity of a large number of steroids to inhibit gonadal function in male rats, it has been observed that the endocrine component of the testis appears to be inhibited more readily than is spermatogenesis. The compound is administered by the oral or parenteral route in 30-day-old male rats for 30 days. This method enables the inve stigators to distinguish between the inhibition of spermatogenic and endocrine functions of the testes and, by extrapolation, between the extent of inhibition of the FSH and ICSH secretory capacities of the hypophysis. Some of the compounds which appear to inhibit ICSH at a lower dose level than is required for inhibition of FSH are 17alpha-ethi nyl-5(10)-estraenolone, 17alpha-ethinyl-19-nortestosterone, 17alpha-ethi nyl-19-nortestosterone enanthate, 17alpha-ethinyl estradiol-3-methyl ether, 9alpha-bromo-11-ketoprogesterone, and 17alpha-2-methallyl-19-nortestosterone. Compounds whose androgenic activity are such that differentiation between ICSH and FSH inhibition c annot be made by this method although their inhibitory effect on total gonadotropin can be shown include testosterone propionate, methyl testosterone, methyl-19-nortestosterone, 17alpha-ethyl-19-nortestosteron e, and progesterone. In applying the findings to the female, it is suggested that the effectiveness of a compound in suppressing ovulation is not so much a factor of total gonadotropin inhibition as it is of an upset of the ICSH (or LH) and FSH balance. The FSH-LH ratio must be disturbed to a degree that follicular maturation and rupture are unable to progress normally. This would explain the observation that some relatively poor gonadotropin inhibitors, such as progesterone, have been observed to suppress ovulation.(AUTHOR'S, MODIFIED)
5- and 10-year results of 460 patients treated for breast cancer at the Johns Hopkins hospital during 1951-1956 are reported. Follow-up was obtained in all but 1 patient. 274 were Caucasian, 186 non-Caucasian, and the median age was 52 years. Radical mastectomy was done in 370 cases, simple mastectomy in 54 cases, and a modified radical operation in 8. The other 28 had only biopsy. Operative mortality was 1%. About 40% had negative axillary nodes, 47% positive nodes, 13% unknown. The 5-year crude survival rate for radical mastectomy was 62.3% and the 10-year crude rate 48.7%. The prognosis for Negro women was worse, even when compared to stage of disease. Compared with earlier reports, the Johns Hopkins figures were 20% better in the survival of patients with localized disease but only 10% better in patients with regional node involvement. World-wide survival rates are similar regardless of differences in type of treatment, which leads investigators to believe that factors of intrinsic malignancy of the tumor vs. intrinsic resistance of the host may be more important in the final outcome than differences in treatment. Studies are needed to assess the value of adj uvant therapy including castration, preoperative or postoperative radiation, and chemotherapy.
Relation of various epidemiologic factors to cervical cancer as determined by a screening program.
This study attempted to elucidate the etiology of cervical cancer by examining its association with a number of factors in a relatively unselected group of women. In 1963, a cytologic screening program was undertaken in Washington County, Maryland. The irrigation smear method was used. The final study group of 4341 was 46% of all white women aged 30-45 years enumerated in the census. Of the 4290 satisfactory smears, 46 were positive or suspicious. Subsequent investigation confirmed 31 cases of which 28 were at Stage 0 and 3 were invasive carcinoma of the cervix. Of 15 with suspicious cytologic findings 6 had confirmed findings, all of which were at Stage 0. Women who were never married had no confirmed cases. Currently-married women had lower rates than women whose marriages had been disrupted. Those who were married at age 16 or earlier had higher rates of cervical cancer as did those from lower socioeconomic levels. Having had multiple sex partners was associated with an increased risk of developing cervical cancer. Smokers had slightly higher rates than nonsmokers. Trichomonas vaginali s infestation was associated with higher rates. Findings indicate that trichomoniasis and cervical cancer are both associated with sexual activity.
Endometrial morphology and polyethylene intrauterine devices: a study of 200 endometrial biopsies.
209 consecutive endometrial biopsies were taken from patients at the Contraceptive Service of the Margaret Sanger Research Bureau in New York City. Patients had used polyethylene IUDs from 1 day to 105 months. IUDs used were Lippes loops B, C, and D (147 biopsies), Margulies coil 5 (28), Birnberg bow 3 and 5 (21), and more than 1 type (13). 96 of the patients were asympotomatic; 112 had IUDs removed because of abnormal or excessive bleeding, pelvic pain, persistent vaginal discharge, or anothe r symptom related to the presence of the device. The mean ages for asymptomatic and sympotomatic patients, respectively, were 32.3 and 32.0. The mean periods of use for the asymptomatic and symptomatic groups were 30.1 and 20.7 months, respectively. Since 9 of the biopsies yielded insufficient tissue for examination, the observations were based on 200 biopsies from 199 women. The 3 classes of endometrial biopsies were normal, minor changes, and significant lesions. 29% of the 106 biopsies from symptomatic patients and 40% of the 93 biopsies from asymptomatic patients were interpreted as normal. Minor changes were either local and superficial endometrial reactions of minor degree or asynchrony by 7 days or more from the stated day of the cycle (arbitrary 28-day basis) on which biopsy was obtained. 45% of the biopsies in symptomatic patients and 50% of those in asymptomatic patients showed minor changes. Among the minor changes in both asymptomatic and symptomatic patients, the ratio of minor-stromal-reaction biopsies to as ynchronous biopsies was 1:2. Biopsies designated as having significant lesion were those showing a diffuse inflammatory process or another intrinsic endometrial abnormality. Among 107 biopsies from symptomatic patients 25.2% had significant lesions. Among Lippes loop users 28% and 12.5%, respectively, of symptomatic and asymptomatic women showed significant lesions. Lesions were absent in the 28 women using Margulies coils. The number of patients using the bow was too small to provide relevant data. The main type of lesion found among Lippes loop users was endometritis, chronic or acute. 2 of the total of 13 biopsies having chronic endometrit is also had squamous metaplasia of the surface epithelium covering fundic endometrium, suggesting that long-term study of women using polyethylene IUDs is a good idea.
Projected world population and food production potentials.
During the past 200 years a technological revolution throughout the world has continuously improved the levels of living in rich countries, but in poor ones its principal effect has been to multiply human misery by causing a rise of human population at rates higher than ever before experienced. The rate of population growth was about .5% a year until 1900 and nearly 1% to 1950. Now rates are about 2% a year and in some countries 2.5-3%. At this rate the world's population now doubles in about 30 years. This growth and the lag in economic and social development are interrelated. For the next 20 years it is necessary to bring about an unprecedented increase in world food supplies because no likely reduction in population growth in poor countries will be adequate. Moreover a marked improvement in human diets, especially for infants and children, may be essential to lower birthrates because the availability of contraceptive devices may be unimportant until the desired number of living children is secured. Although the population p roblem has been created by lowering death rates, an essential element in overcoming the problem is to lower infant and child death rates still further. Increased production in developed countries cannot be adequate to supply poor countries 20 years hence. Although the cultivable area of the world is over 2 times as much as actually cultivated, the cost of bringing such lands into production is not economical. Most are in the tropics and methods of cultivating food crops in these areas on an intensive scale have not been developed. Long-term programs, capital assistance, and technical assistance will be needed on a large scale. Industry, universities, and research laboratories must cooperate. Some achievements have been made. Mexican wheat varieties in Pakistan and India and new rice varieties from the Philippines are promising. Other fertilizer-responsive crops have been planted in India. Availability of capital and introduction of new technology are needed. However, overall foreign aid effort to date has been too little and sometimes too late.
Relationship of family planning to pediatrics and child health.
This article starts from the premise that there are good reasons as to why family planning and child health services should be closely related to each other, in the end helping prolong the life of the infants, promote optimum levels of growth, and better the quality of par ental care. The points discussed in those terms are: 1) greater intervals between pregnancies reduces the chance of infant and child mortality, 2) family planning helps better the quality of family life and the health of the existing children by keeping the number of children low and the intervals between them optimum, 3) infant and child mortality reduction is a prerequisite in many underdeveloped countries for couples to adopt family planning, 4) family planning education and services should be a part of school programs, 5) large family size and overcrowding are associated with children's diseases, 6) children of large families are smaller in size, 7) maternal care in large families is less adequate than that in smaller families, 8) because of less maternal supervision, accidents in childhood may be more in the large families. The authors feel that family planning and child care services should be brought together for the foregoing reasons. The ways of doing this may include special health programs for school children, dissemination of family planning information in day care centers, head start programs, and diagnostic, counseling, and treatment centers for handicapped children, etc.
Contraceptive methods applied in family planning clinics in Egypt.
To avoid the use of criminal abortion as a means of family limitation in Egypt, 12 family planning clinics were established in various communities. The mechanical methods used were diaphragm and jelly, cervical cap and condom. Chemical methods included jellies, creams, suppositories, and foam tablets. In addition combination methods such as diaphragms with jelly, sponge with either 10% salt solution or a contraceptive or medicated tampon were used as well as physiological methods. Diaphragm and jelly was the most satisfactory method used and the most accepted. Because of the popularity of the method, a diaphragm suitable for use by the Egyptian women in a tropical climate is being produced locally with resulting economic advantages for the Egyptians.
Brief talk on the work of the Family Planning Association of Great Britain.
The Family Planning Association of Great Britain (FPA) receives no h elp from the British treasury but, since 1956, the government has at least recognized the good work done by the Association. The recognition has meant that information could be aired through the public media. The FPA works to establish clinics throughout Britain, sometimes using Public Health facilities if available. 235 clinics are currently in operation and more are needed. The London headquarters of FPA runs a pregnancy diagnostic center, a section on male subfertility, and research to test new contraceptives.
How are we doing in family planning in India?
The proposed family planning goal of the government of India is to r educe the birth rate from 41 to 25 per 1000 by 1975-1976 and to 22 by 1978-1979. The author describes 3 ways in which this could be done: 1) concentrating all efforts in the first year; 2) concentrating all effort s in the last year; and 3) making efforts to reduce the birth rate linea rly. The total population at the end of 1975-1976 would be respectively 559,000,000, 644,000,000, and 600,000,000. The total number of births to be prevented from 1966-1967 to 1975-1976 would be 85,300,000; 10,200,000; 49,200,000.
Pseudopregnancy: treatment of periodic psychiatric illness: a pilot study.
Although the use of oral contraceptives has been implicated in the onset of depressive episodes, pregnancy has been noted to be associated with a lower risk of developing periodic depression. It was considered worthwhile to pursue a small pilot study to evaluate the potential gain or risk of treatment with Enovid, an agent that at high dosage produces a pseudopregnant state. Patients were selected who had a history of periodic psychiatric illness or postpartum depression. Initial psychiatric evaluation and medical studies were done. The drug regimen used was 10 mg Enovid for 1 week, with weekly increments of 10 mg until 40 mg were reached. The drug was then discontinued and a placebo given for 2 weeks. Patients were observed for another month. Psychotherapy, occupational, and recreational therapies were continued during the treatment period. Of the 4 patients studied, 1 improved moderately, 1 slightly, and 2 remained unchanged. Clinical use should be deferred until further data are accumulated.
Low-oestrogen oral contraceptives.
The authors wrote in response to an account by Dr. E. Grant of sympt oms occurring in patients taking low-estrogen oral contraceptives (OCs). They reported a study of 60 patients enrolled in a "side effects" study of Ortho-Noven 2 mg (norethisterone 1 mg plus mestranol 100 mcg) later changed to Ortho-Novin 1/50 (norethisterone 1 mg plus mestranol 50 mcg). After 363 cycles on the low dosage, 29 patients reported markedly reduced vaginal bleeding (8 had pseudoamenorrhea), 7 had slight breakthrough bleeding and 4 had premenstrual pain for the first time. It was felt that these side effects differed from those reported by Dr. Grant because she used 5 quite different formulations representing a variety of estrogen/progestogen combinations whereas in this study the ratio of estrogen to progestogen remained the same. In this study no patient found the side effects sufficient to stop taking OCs.
Industrial pressure and the population problem the FDA and the pill.
Contrary to expert testimony before the Nelson Committee, Enovid was not approved by the Food and Drug Administration because of "industrial pressure." In 1959 neither G.D. Searle and Company nor the FDA wanted to become associated in the public mind with contraceptives. Both were unduly careful. Enovid had been in use for treatment of endometriosis and hypermenorrhea for 3 years before the company applied to market it as a contraceptive. The application was accompanied with data on 897 women who had taken the drug through 10,427 cycles. At the time, estrogens and progesterone were not considered dangerous drugs. Outside authorities were consulted before the FDA granted a "no objection" status to Enovid.
Reaction of unmarried girls to pregnancy.
An article by Claman, Williams, and Wogan in the Canadian Medical As sociation Journal reports their study of 316 unwed clinic patients at Vancouver General Hospital. 85% were between 16-25 years old, most under 20. Their reactions to the pregnancy were 1) fear of parental rejection; 2) fear of financial hardship; and 3) immediate thought of marriage. Most rejected marriage as an alternative, an enlightened response compared with former times. Most received supportive help from parents. Few chose abortion. More than 1/3 had been pregnant before. The authors concluded that once a young girl becomes pregnant out of wedlock, she is likely to do so again.
Administrative evaluation: an overview.
This paper focuses on the administrative aspect of evaluation of family planning programs such as assessing the organization of family planning clinics rather than measuring the economic effects of a family planning program. In a sense, administrative evaluation is more limited and more focused that overall family planning program evaluation. The exact questions that are being asked will determined the nature of the evaluative process. The author defines the administrative evaluation as evaluation of the action oriented, operational aspects of a program. As well as being program oriented, administrative evaluation is also task and activity oriented. It operates on a set of basic assumptions such as improvement in program operations leads to better utilization of services which may then have an effect on knowledge of, attitude toward and practice of the services. The characteristics of a useful evaluation, according to this article, are simplicity, practicality, uti lity, inexpensiveness, promptness, acceptability. Another part of the paper focuses on family planning administration and its evaluation in terms of answering questions such as determining who comes and who continues.
Estimating fertility without good vital statistics.
In discussing how to estimate fertility in the absence of good vital statistics, this paper elaborates on 5 different methods of fertility estimation. The first one, the reverse survival method, requires a life table describing the mortality situation at the time of the census. With this method it is possible to estimate fertility measures from basic census age data. The second method is called the "own children technique" based on census of survey data on own children who live with their mothers. The third method, the Brass technique, is a way of estim ating fertility from reports on childbearing in the past. Fertility rates are computed by using the census or survey data on children ever born and births by age of mother in 1 year preceding the census or survey. The Pregnancy History Analysis, the fourth method suggested, is based on a battery of interview questions serving as a substitute for vital statistics registration. The Population Growth Estimation (PGE) study, the fifth method considered, requires that the vital events be recorded by 2 independent investigators in sample areas. The article elaborates on the specifics of use of these methods and suggests that the Brass technique not be used on populations whose fertility has changed drastically in the recent past. The Pregnancy History Analysis approach works well if a good sample design is developed. The PGE, on the other hand, may require too much time and expense.
Sex-age pattern of population mobility in the U.A.R. with some international comparisons.
Egyptian census information collected since 1907 provides basic data on population mobility in the country over a long period of time. The general population is almost equally balanced between males and females. Males migrate slightly more than females do. Only in the depression period of 1927-1937 did female exceed male migration. The distance of migration affects the sex composition of the migrants; males migrate longer distances. This is also true in other countries. Age composition of major urban areas is similar in the countryside. The proportion of children under 15 in Cairo in the 1960 census was exactly the same as in the country as a whole. Young adult males do seem to migrate more than other age-sex groups. Economic prosperity tends to encourage migration for both males and females. Rural-to-urban migration seems to be fairly permanent, except when hard economic times hit. Retired people do not seem to return to the countryside.
The natural history of untreated breast cancer.
This report on breast cancer between the years 1805 and 1933 was obtained primarily from the early Middlesex (London) Hospital Cancer Cha rity records. Of 356 cases cared for in the hospital during this period, records were adequate for 250. Almost all were advanced cases o n admission. All died in the hospital. Autosies confirmed the diagnoses in all cases. Histopathological material was still available for 86. In these the incidence of tumors of low-grade malignancy was identical with that found in present-day cases. None had been treated with surgery or radiotherapy. At 3 years 44% were alive, at 5 years 18%, and at 10 years 4%. All had died by 19 years although 9 patients lived over 10 years. The median survival was 2.7 years. The prognosis was less favorable for young women. Those histologically graded 1 and 2 lived longer than those graded 3. No case of spontaneous regression was observed. A long, drawn-out distressing illness was suffered by many.
Deladroxate for the prevention of ovulation.
The article presents a study assessing the effects of a monthly injection of dihydroxyprogesterone acetophenide (Deladroxate) combined with either 10, 20, or 30 mg of estradiol ethanate in 3 groups of 10 women. Ovulation was entirely inhibited during the interval between shots. A high degree of side effects was observed, e.g., breast tenderness, heavy or prolonged menstrual flow, premenstrual fluid retention, and decreased libido. These side effects have been minimized by using dosages with less estrogen and more progestogen without depriving the drug of its antiovulatory effect.(JPS JPS)
The testes and accessory glands of 4 pubescent and 6 adult monkeys were examined in histologic sections stained with periodic acid Schiff reagent at various times from 17 hours to 7 months after a single sc injection of 1 ml cadmium chloride (9.12 g/l). In pubescent testis removed 17 hours or 8 days after injection, the diameter of the seminiferous tubules had decreased, and the spermatogonia had ceased spermatogenesis, the germinative cells on the periphery were necrotic, but the Sertoli cells were intact. 3 months later some tubules showed necrotic spermatogonia. In adults, 3 weeks after injection, the seminal vesicles, epididymal epithelium and prostate were atrophied. 3 months later the accessory structures had recovered, by 6-7 months approaching controls. During this time, the Sertoli cells were thriving, spermatogenesis was apparent, but newly formed sex cells were degenerating. Some Leydig cells had a large nuclei with prominent nucleoli.
Oral contraceptives have been suspected of playing a causative role in occlusive vascular disease. Women with hypertension, migraine, or va scular disease are thought to be especially at risk. The increased incidence of strokes in young women using the pill has been noted. Although meaningful morbidity data are lacking, complacency is not justified. Many women receiving the pills do not have adequate medical supervision. Observation of those accepting the risk should be careful and continuous. Alternate methods should receive greater attention. Despite unanswered questions, social, economic, and geopolitical factors still warrant this form of population control.
Oral contraception and thromboembolic disease.
Results of 2 case-controlled, retrospective studies on the risk of thromboembolic disease among oral contraceptive users are summarized and evaluated. The British Committee on Safety of Drugs found that risk of death from thromboembolism is 1.5 per 100,000 women annually for previously healthy pill users aged 20-34, compared with .2 for nonusers, and 3.9 for users aged 35-44 compared with . 5 for nonusers of same age g roup. The British Medical Research Council concluded that hospitalization for deep vein thrombosis would be required annually for 1 in 2000 married healthy pill users compared to 1 in 20,000 nonusers. The author recommended that women with predispositions to thromboembolism, such as hypertension or diabetes, not be given oral contraceptives. The risks should be weighed against risk of death from of death from smoking, pregnancy, cancer, and accidents.
Reproduction in goats subsequent to removal of intrauterine spirals.
An experiment was conducted in which female goats were fitted with intrauterine polyethylene spirals in 1 or both uterine horns. Their fertility was tested with the devices in place and after removal and compared with control goats' fertility. The estrous cycle in goats fitted with IUDs was reduced; the cycle returned to normal following removal of the IUD. This is evidence that no permanent endocrine changes are induced by IUDs. Following removal of the spirals, overall fertility of the IUD-fitted goats was 71%, compared to 100% for the control group. This difference was not statistically significant. No uterine pathological changes were induced by the spirals. It would seem that the contraceptive effect of IUDs lasts only while the device is in place.
By 1973, the birth rate in Taiwan will have been reduced from 36 per 1000 in 1963 to about 24 per 1000. The purpose of the policy of continuing the reduction as fast as possible is primarily economic, i.e., raising the standard of living and making increased savings possible. While industrialization, urbanization, and economic growth work for this policy, the increasing fecundability of the population and the significant increase in the number of young women of marriageable ag e are working against it. The achievement in Taiwan to date has primarily been reached by the full-time home visitors. There are advantages to having family planning and the regular Provincial Institute of Maternal and Child Health (MCH) programs work closely; help can be gotten from the experienced MCH personnel. However, when the MCH program is still weak, the family planning program should go ahead without having to wait for the advancement of the MCH program. A major educational effort is needed to reach young people and thereby change th e ideal family norm from 4 to as near 2 as possible. Nutritional education within the MCH program will have to be improved and strengthened also.
Septic abortion: current management.
The management of septic abortion continues to improve. Trends of i mportance are: 1) earlier and improved diagnosis, and 2) prompt and aggressive treatment. Initial treatment must be based upon a clinical diagnosis. A delay in treatment while awaiting laboratory confirmation could permit irreversible toxic processes to become established. Metabolic disorganization resulting from the circulating bacterial toxins can lead to the rapid onset of septic shock and renal failure. Early evacuation of the uterus, along with the rapid administration of p harmacologic doses of proven antibiotics (chloramphenicol, penicillin) and steroids (Solu-Cortef, Solu-Medrol), will give the patient the greatest possible advantage. Total abdominal hysterectomy with bilateral salpingo-oophrectomy in cases of early treatment failure, or in cases of welchii infection, has contributed significantly to the saving of lives.(FULL TEXT)
A novel, practical synthesis of 18-norsteroids.
18-norsteroids were synthesized from hecogenin derivatives by decarboxylation of a 12-keto-18-oic acid. 3beta-acetoxy-20beta-hydroxy-5alpha-pregnane-12-one, a hecogenin derivative, was treated with lead acetate and iodine in cyclohexane, yie lding a gamma-lactone as the main product. The lactone, when treated with dilute NaOH in methanol gave the 18-nor-3beta-acetoxy-20beta-hydroxy-5alpha-pregnane-12-one. The rings structure was verified as 13beta,14alpha trans, by comparison of the IR spectrum with that of a pure sample.
Stroke, sickle cell trait, and oral contraceptives.
A case report of a woman who developed a positive sickle cell test a nd an A-S pattern with less than 2% hemoglobin F (hemoglobin electrophoresis) while taking the oral contraceptive Ovulen (1 mg ethynodiol diacetate and .1 mg mestranol) is presented. Since 8.5% of American Negroes have sickle cell trait, it is suggested that a sickle cell test and a hemoglobin electrophoresis be performed before prescribing an oral contraceptive for a Negro patient. An alternative contraceptive method is suggested if sickling or hemoglobin S is found.
Contraceptive pill and thyroid nodule.
A case report of a 30-year-old twice gravid female who developed a h yperfunctional, thyroid-stimulating hormone-dependent thyroid nodule whi le taking an oral contraceptive agent is presented. While the drug was maintained, the nodule grew larger; but when the drug was discontinued, the goiter decreased in size and then disappeared. The association of an oral contraceptive drug and a nodular goiter may be coincidental, but a causal relationship involving thyroid-stimulating hormone should not be ruled out. Careful examination of all women taking oral contraceptive steroids and frequent radioactive thyroidal scans may bring to light a number of such cases that perhaps are being overlooked.
The statement of H.H. Suter (Letters, May 15) that "abortion, culling, (and) termination" will cover population control concerns only one side of the ledger. The other side - a new worry - is the generation of selected individuals. One can visualize the use of somatic cells or cultured somatic cells for the replication of larger numbers of "superior" beings. Several techniques that could make this feasible will be available in the near future. It is now possible to maintain or preserve the genetic pattern of somatic cells - how perfectly isn't known - of an individual long after his death. From an ethical and "moral" viewpoint perhaps we should take steps to insure that an individual's genetic pattern is not replicated as an individual and dies with him.(FULL TEXT)
Failures in natural conception control and their causes.
This summarizes case histories of 59 women who became pregnant while using the Ogino-Knaus method of biological birth control (rhythm system) . There were 2 actual failures, 23 women erroneously had intercourse during the conception period, 13 kept insufficient menstrual records before starting (less than 4 months), and 14 women used the method without any menstrual record at all. 2 women used the method immediately after childbirth before the menstrual cycle had reestablished itself. There was 1 irregularly menstruating woman, 1 with inflammation of the cervix, and 3 with pregnancies due to mental shock, change of climate, or marked variation in physical habits. Records of 11,222 intercourses from 265 women during the sterile period show no conceptions, confirming this method is practical and reliable when used correctly. However, adequate menstrual records must be kept before beginning. Although the menstrual cycle may be temporarily upset by sickness, physical or mental shock, unusual exertion, great change of climate or altitude, or other distrubances, it usually returns to accustomed regularity after the disturbance is past.
Anastomosis of the vas deferens to correct post vasectomy sterility.
It is emphasized that anastomosis of the vas deferens has been succe ssful in a sufficient number of cases to justify its more frequent perfo rmance. In 6 cases operated on by the author, normal sperm counts were later found in 5. Also, in 1 case with tuberculous epididymitis, a normal sperm count followed resection of the diseases tissue. Vasectomi es of these patients had been done from 3 to 13 years previously. In 1 successful case, a previous unsuccessful operation had been done elsewhe re to correct the condition. An intraluminal splinting silkworm suture was used in each case. This was removed after 4-6 days. Minimal dissection and gentleness was used in handling tissues. Mattress-type sutures were placed to retain approximation of vas ends with minimal tension. Very fine silk sutures were used at the anostomoses with care taken to avoid penetrating the lumens. The operation is recommended in selected cases.
Chlormadinone, a potent synthetic oral progestin: evaluation of 1002 cycles.
A clinical evaluation of chlormadinone acetate, a synthetic steroid preparation with marked and selective progestational effect on the endom etrium, is presented. Like progesterone it demonstrates no estrogenic activity; in fact, it is a potent antiestrogen and requires either endogenous or exogenous estrogenic priming of the endoemtrium to produce secretory effect. It does not show androgenic properties that might predispose either the patient or her female female to masculinization. 279 patients were followed for 1002 menstrual cycles. 143 received various dosages either alone or in combination with mestranol for either primary or secondary sterility lasting from 1 to 10 years; 90% had sterility of 2 years or more. These women were treated for 451 cycles. Withdrawal bleeding occurred within 7 days of cessation of therapy in 79.5% of cycles; in all but 5 of the remaining cases bleeding occurred within 14 days. The oral contraceptive group consisted of 130 women who took 80 mcg mestranol daily from Cycle Day 5 to 19 followed by 2 mg chlo rmadinone and 80 mcg mestranol taken from Day 20 to 24. 15 patients rec eived a hemogram, a clotting profile, routine urinanalysis, and a battery of liver, thyroid, and adrenal function tests as well as endomet rial biopsy at 3-6 month intervals. In 98.7% of all cycles withdrawal bleeding occurred within 7 days; in 4 cycles there was pregnancy and in 2 patients failed to follow the regimen properly. 8 patients experienced prolonged menstrual flows and 1 markedly diminished flows. No adverse effects were found in any of the laboratory examinations. 6 patients were selected for special study while on chlormadinone therapy. In 3 with secondary amenorrhea investigators found secretory endometrium; in 3 with normal menstrual cycles, regressive glandular changes with pseudodecidualization was found. Undesirable side effects included breakthrough bleeding, some nausea (although less with chlormadinone alone than when combined with estrogen), mastalgia, and dysmenorrhea. No cases of thrombophlebitis or pulmonary embolism were observed. Doses of 2-4 mg proved adequate to stimulate normal secretory endometrium with predictable withdrawal bleeding.
Population growth: challenge to endocrinology.
The basic population problem is the decreasing quality of life of human numbers. The rate of growth of 2% per year is unprecedented and largely due to decelerating death rates in countries with low living standards and high growth rates (up to 3%). These countries are trying to increase economic growth but need to invest a 9% increase in capital just to maintain their 3% annual growth. The problem is augmented for them because over 40% of their numbers are children dependent for health care, education and consumer items. The economists debate whether famine will come soon or whether we will find barely enough food eventually; the poor countries can discuss whether their next doubling will occur within 60 years rather than 25. These countries cannot wait for economic, medical and educational development to slow their population growth. Although all couples are free to plan or limit their families, many of them, e.g. 80-85% of the people in Africa and South American have no national family planning programs. Over 9% of the effective contraception in Asia is due to IUDs and sterilization. In many countries pills have not been used, but studies have shown poor continuation rates, e.g. 41% after 1 year. The reason is probably that hormonal contraception needs a better technology, an acute challenge to endocrinologists.
Low-dose progestagens as contraceptive agents.
The low dose progestogens available for use as contraceptive agents are identified, and the evidence of their possible mode of action is discussed. The relative acceptability and clinical effectiveness is also indicated. Progestational agents fall into 2 groups: 17-acetoxy progestogens (chlormadinone acetate 500 mcg and megestrol acetate 500 mcg) and 19-norsteroids (norgestrel, 50-75 mcg, norethisterone acetate, 300 mcg, norethisterone 500 mcg, and ethynodiol diacetate 250-500 mcg). The effect of the progestational agents on the hypothalamo-pituitary-ovarian mechanisms can be interpreted from leutinizing hormones (LH) levels. 17-acetoxy progestogens disturb LH excretion and the dose of these drugs which inhibits ovulation is very close to the dose exerting local contraceptive action. In 19-norsteroids administration, the LH midcycle surge is still present but long-term use may distort the LH peak rather than suppress it. 19-norsteroids seem to effect the ovarian function, although the corpus luteum appears normal. Evidence for an ovarian effect produced with chlormadionone acetate is less convincing. An effect of these progestogens on the endometrium appears to be absent, however, this assertion is without the support of electron microscopy study. Cervical mucus is a major site of action of the 17-acetoxy group although this may be unrelated to contraceptive effectiveness. The data on the effect of 19-norsteroids on cervical mucus is conflicting. Animal studies with low dose progestogens have shown unusual findings to be absent, although breast nodules were found in the beagle. The disadvantages of the low dose progestagens are in the irregular bleeding and the use effectiveness rate of 9/100 woman-years and method failure of 6/100 woman-years.
A technique of vasectomy for sterilization.
A technique used in 160 vasectomies is described and illustrated. After injection of novocain, short incisions are made, the vas is graspe d with a hook, freed from surrounding tissues, and 1 or 2 inches excised. The proximal end is ligated with dermal sutures and buried in the surrounding fascia; the distal end is ligated with catgut and anchored outside the fascia using a dermal suture. Patients reported for sperm checks until semen was spermatozoa-free. In 2 cases efforts were made to reestablish patency. In 1, done 7 years and 8 months after vasectomy, the outcome seemed successful. In the other, done 7 years after, the outcome was not.
The clinical effectiveness of the rhythm method of contraception.
Of 551 women referred to the rhythm clinic at the Free Hospital for Women in Brookline, Massachusetts, 409 used the method for 1 month or longer. They were observed for 7267 months or 605.6 woman-years. 224 participated for less than 1 year, but these patients contributed only 1134 months or 15.6% of the aggregate exposure to the risk of pregnancy. The number of accidental pregnancies recorded during this period was 57. In addition, 209 women discontinued participation without further contact with the clinic. To determine if additional accidental pregnancies were concealed in this group, a trained social worker contacted a selected sample of 69 women and found 10 (14.5%) who were accidentally pregnant when they withdrew from the clinic. If this ratio is applied to the 209 nonreturning patients, the estimated concealed pregnancies is 30, for a total number of accidental pregnancies of 87. This gives a rate of 14.4 pregnancies per 100 woman-years of exposure or 1 unwanted conception for 8 years' reliance on the method. This is much higher than the rates for diaphragm-and-jelly or condom (6 or 7 per 100 years of exposure). For those for whom pregnancy would be dangerous, this method is considered inadequate.
Steroids. 12. Aromatization experiments in the progesterone series.
Aromatization experiments in the progesterone series are presented. Mineral oil vapor phase aromatization was employed in converting 1,4,16- pregnatriene-3,20-dione, prepared from allopregnane-3,20-dione, into 3-hydroxy-17-acetyl-1,3,5,16-estratetraene. Reactions discussed included its transformation into the aromatic analogs of the corpus luteum hormone progesterone, and the adrenal hormone 17alpha-hydroxyprogesterone. Progesterone or 16-dehydroprogesterone on tri- or dibromination, respectively, followed by collidine dehydrobromination, lead to the same 1,4,6,16-pregnatetraene-3,20-dione which undergoes the dienone-phenol rearrangement. Hydrogenation of the rearrangement product yields the aromatic progesterone analog 1-methyl-3 -hydroxy-17-acetyl-1,3,5-estratriene.
Some effects of progesterone and related compounds upon reproduction and early development in mammals are described. The efforts were largel y directed toward studies designed to induce progesterone effects at critical stages during the follicular phase of the cycle. In humans, ovulation-time studies were based on the examination of the temperature curves, endometrial biopsies, and vaginal smears taken during control cycles. In the experimental cycles, positive diagnosis for ovulation time was possible in 27% of the temperature curves, 18% of the endometrial biopsies, and 6% of the vaginal smears. The incidence of ovulation time practically coincides with the incidence of mature corpora as revealed by laparotomy. Pregnanediol excretion studies suggest that progesterone taken orally may be excreted in the feces or that if it is absorbed via the enterohepatic circulation, a liver-produc ed metabolite other than pregnanediol is produced, which may or may not be the "effective" ovulation inhibitor. Follow-up studies revealed a rapid return to normal ovulation cycles following progesterone discontinuation. The effects of 19-nor-17-ethinyl testosterone and 17-ethinyl estraeneolone were examined in a limited number of humans. Their effects appear to be more potent and more promising than progesterone. The nonsteroidal substances, cirantin and metarylohydroquinone, were studied in rabbits and in rats. No marked antifertility action was observed in rabbits at dosages the same as or larger than those found effective with 15 active steroids, but both were effective in the rat. The deductions made from these studies are that 1) a number and variety of substances capable of preventing fertility in experimental animals are demonstrable, 2) certain substances having ovulation-inhibiting effects in experimental animals exhibit entirely comparable effects in the human female, and 3) effective substances may be taken by mouth or administered parenterally.
Religious factors in the population problem.
The Roman Catholic Church has often been singled out as the sole religious opponent of efforts to reduce birth rates. Other major religions do not officially condemn contraceptives. Moslems have official permission to practice contraception but their birthrates are uniformly among the highest in the world. The disparity between official doctrine and actual behavior exaggerates the importance of Catholic doctrine. The influence of religion as exerted through promulgated doctrines is not as important as fold beliefs. Desired family size is nearly always larger in undeveloped countries. To achieve replacement levels birth rates in most underdeveloped nations need to be reduced 50%; contraceptive control without changes in motivation cannot bring about such a change. Reductions in infant and c hild mortality, urbanization, industrialization, and associated economic factors as well as religion relate to these inducements. Recent Catholic thought tends to stress that family size must be determined by the family in its own circumstances and not by social or political agencies or even by the Church. However, the Church does promote the moral desirability of large families when within the means of the couple. Spacing, as a form of planning, has religious sanction because it helps safeguard the health of the mother. Folk beliefs, religious or otherwise, are a significant point at which religious variables become r elevant in predicting ways motivation to control fertility can be increased. A pronatalist factor in Islam stems from a strong belief in the active providence of Allah. Any question of restricting the number of offspring tends to appear as lacking in piety. In the popular minds of Hindus and Buddhists the conscious endeavor to prevent conception, other than by abstinence, has often been interpreted as injury to life and as interference in natural and morally inviolable cosmic processes. Communists adhere to the Marxian assertion that overpopulation per se can never exist in a socialist state and that inequity in resources is a consequence of capitalistic production. However late marriage and sanctions against having more than 2 children are used in China. Russia maintains that population growth is within the scope of governmental authority. The Catholic insistence upon the voluntary nature of family-size decisions is considered favorable. In all cultures the voluntary approach is considered the best.
Oral contraceptives and urokinase activity.
The effect of oral contraceptives (OCs) on the excretion of urokinase and the patterns of urokinase excretion in normal women during the menstrual cycle were studied. Urokinase activity was determined on morning specimens by the Von Kaulla method. The results indicated an increase in urokinase activity as a result of OC use. The mean optical density of urokinase activity in urine of users was .886 as compared with .372 for nonusers. There was wide variation in urokinase activity among normal women within the same menstrual cycle phase and only a slight change (increasing toward the end of the cycle) in any given individual throughout the cycle.
The effect of ethinyl estradiol, medroxyprogesterone acetate, and 3 oral contraceptive preparations (Enovid E, Enovid, Provest) on experimen tal allergic encephalomyelitis (EAE) was studies. .005 mg/day ethinyl estradiol prevented the development of EAE in rats immunized with .2 mg of 10% rat cord in Freund's adjuvant. 8 of 10 controls showed histologic EAE at sacrifice 3 weeks postimmunization; in 6 it was severe. 2 of 9 ethinyl estradiol-treated rats showed histologic EAE, and in only 1 was it severe (p greater than .01). Clinical disease was inhibited, and the treated gained while the controls lost weight. 1 mg medroxyprogesterone acetate did not inhibit EAE in rats immunized with 10% rat cord. 14 of 17 treated showed histologic lesions (11 were severe), which was comparable with the untreated controls. 21 of 31 controls showed clinical disease, whereas all 17 treated rats showed clinical disease, indicating medroxyprogesterone acetate exacerbated EAE. The 3 combination OCs all inhibited EAE at 3 weeks in rats immunized with 10% rat cord. When kept for 6 weeks, Enovid E and Enovid groups remained disease-free, whereas 8 of 11 treated with Provest showed disease. Since EAE mimics multiple sclerosis (MS) clinically and pathologically, the question of whether women with MS should be given OCs arises frequently. It was suggested that those OCs with the highest estrogen-to-progestin ratio be favored in patients with MS.
Inhibition of HCG-induced ovulation by anti-HCG serum in immature mice pre-treated with PMSG.
The minimum time in which ovulatory gonadotrophin must be present in the circulating blood of the mouse to be effective was determined. Mice received a subcutaneous priming injection of pregnanct mare's serum gona dotrophin (PMSG) followed by a single subcutaneous or intravenous inject ion of human chorionic gonadotrophin (HCG) 54-56 hours later. Rabbit anti-HCG and -PMSG were injected at various times after the injection of the ovulating hormones HCG and PMSG. The mice were sacrificed 20-24 hours later for the examination of tubal ova. Ovulation was completely blocked when the hormone and its antiserum were administered simultaneously by intravenous injection. All mice ovulated normally when the injection of antiserum was delayed for 2 hours. It was concluded that a 2-hour existence in the circulating blood is sufficient for the ovulatory gonadotrophin to induce maximum ovulation and that irreversible changes occur in the mature follicles during this period.
The General Assembly of the International Union against the Venereal Diseases and Treponematoses was held in Budapest in June 1969. Papers dealt with the following topics: 1) changing patterns of sexual behavior and their relation to venereal disease (VD); 2) the need to diagnose and treat VD in routine gynecological examinations; and 3) venereology training. Many countries expressed an interest in the social, educational, and public health aspects of VD. There is a need for the more developed countries to aid less developed countries in venereology training. The modern factors of urbanization and migration of labor are causing a breakdown in the family unit and an increase in VD. "Repeaters" must be studied. Basic biological research is needed. It was mentioned that the increasing use of IUDs and pills, rather than the older barrier contraceptives, is causing a rise in the incidence of VD. All medical and social indications are that VD will continue to rise. Greater financial support for international work in this area is needed.
Recurrent polyneuropathy with pregnancy and oral contraceptives.
This is a case report of a 26-year-old patient with recurrent symmetrical polyneuropathy with 3 consecutive pregnancies and while taking oral contraceptives. She was admitted to the hospital complaining of numbness of hands and feet and progressive weakness of all limbs. Similar symptoms had occurred during 3 previous pregnancies and had progressed to quadraplegia with areflexia. The pregnancies ended in normal deliveries. In the first pregnancy symptoms disappeared in 2 months; in the subsequent ones symptoms appeared earlier and required 6 months to disappear. After the third pregnancy she received for 9 months a chlormadinone acetate and mestranol contraceptive, then ethynodrel diacetate and mestranol. 2 months later symptoms began and progressed in 1 month to complete quadriplegia. She stopped the contraceptive as soon as symptoms began. There was no pregnancy, no cranial nerve involvement, nor muscle atrophy. Distal hypalgesia and decreased position and vibration senses were noted. Nerve conduction velocity was diminished. Muscle biopsy was normal. Nerve biopsy showed degeneration of the myelin sheath with relative preservation of axons. Laboratory tests were normal except for elevated spinal fluid protein. Recovery was slower than previously. After 2 years slight foot-drop was present. There seemed to be a relation between female hormones and the recurrent disorder. The possibility that immunopathologic factors were involved was considered.
Effect of an oral contraceptive agent on blood pressure response to renin. (34640).
This study attempted to determine why an occasional patient develops hypertension that appears to be related to the use of oral contraceptives. Changes in the renin-angiotension-aldosterone system have been blamed. Renin, an enzyme from the kidney, acts on renin substrate, a plasma protein, to release angiotensin, a powerful vasoconstrictor and stimulator of aldosterone secretion. The concentration of renin substrate has been shown to be increased by estrogen. In this study 20 Holtzman albino female rats were treated with norethynodrel with mestranol (Enovid R), given in their diet at .1 mg/kg/day. 20 other rats received 1 mg/kg/day. There were 20 controls. After 3 weeks of therapy, cannula were placed in the femoral arteries and jugular veins. Angiotensin, .12, .25, and .50 mg/kg, was administered iv and blood pressure response recorded in 10 animals from each group. Blood pressure response to renin was determined on the remaining animals. (Amounts of renin giving a response approximately equal to the 3 dosages of angiotensin were used.) Rats given 1 mg/kg/day of Enovid had a significant decrease in blood pressure (p less than .01) to the .5 mcg angiotensin. The .1 mg of Enovid had no effect on blood pressure. All doses of renin produced an increase in blood pre ssure response in rats treated with 1 mg/kg/day of Enovid (p less than .01). Those treated with .1 mg/kg/day had slightly decreased blood pressure response. Angiotensin responsiveness was shown to be decreased when renin was increased. Data indicate that renin-substrate is rate-limiting in vivo in blood pressure response to exogenous renin. However, renin levels may not give a true guide to angiotensin production. As angiotensin responsiveness can be reduced by oral contraceptive agents, determination of angiotensin levels and responsiveness is necessary before the role of changes in the renin-angiotensin system in the genesis of oral contraceptive hypertension can be evaluated.
Contraceptives and hypertension.
Though described in 1962 the hypertensive effect of oral contraceptives was not given much attention until 1967. Since then an increasing number of single and multiple case records have been reported, particularly in an accelerated malignant form. The blood pressure rise may begin weeks or months after beginning such therapy, usually falling by 4 months after therapy is stopped. Estrogen is blamed. Failure of plasma renin to be suppressed has been thought to indicate susceptibility. Estrogens are known to increase the protein substrate upon which the enzyme renin acts to produce the pressor substance angiotensin. The increased angiotensin should suppress the release of additional renin. Failure to do so results in a rise in renin levels and more angiotensin with hypertension. Development of a diagnostic procedure for the early recognition of susceptible patients is suggested. Also the need to occasionally measure the blood pressure of patients taking oral contraceptives is emphasized.
Bacteriological study on the users of intrauterine contraceptive devices.
This study was undertaken because of reports that IUDs might lead to pelvic inflammatory disease. Bacteriological examinations were carried out on 180 women wearing IUDs for periods of 3 months to 13 years. Also 60 non-IUD users were studied. Cultures were incubated at 37 degrees C. on 6 different media by both aerobic and anaerobic methods. Incidence of positive endometrial cultures among the controls was 3.33%; among the IUD users, 6.67%. Bacteria in all cases were few. Corynebacteria, anaerobic bacteria, and Gaffkya tetragena were found. Highest incidence was found in women using the IUD less than 1 year. All users for over 5 years had sterile uteri. Also 23 uteri removed because of cervical erosion or myomata were sterile. The incidence of bacterial growth was higher in the secretory pha