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Geneva, Switzerland, WHO, 1965. 19 p. (WHO Technical Report Series No. 304)This WHO technical report focuses on the 1) psychosomatic factors in human reproduction; 2) hypothalamo-hypophyseal system; 3) mechanism of sexual rhythm; 4) nervous influences on the hypothalamus; 5) hormonal influences on the hypothalamus; 6) neuroendocrine aspects of sexual behavior; and 7) effects of drugs on reproduction. After summarizing current research status on the above-mentioned topics, the following research needs are suggested: 1) assays of individual human endogenous gonadotropins, suitable for clinical application; 2) autoradiography, fluorescent-antibody, spectrophometric interference and histochemical and biochemical techniques for studying cells that supply axons to the primary capillary plexus of the hypophyseal portal system and for studying effects of different hormonal status on hypothalmic structure and function; 3) computer techniques for evaluating electrophysiological data; 4) improved lesioning techniques; 5) comparative studies of reproductive activity patterns, exteroceptive factors, neuroendocrine factors in sexual and related social behavior, and long-term or delayed effects of drugs administered during gestation on subsequent sexual development; 6) studies of synaptic connections of hypothalamic neurones; 7) studies of endogenous gonadal and gonadotropin production in prepuberal animals; 8) functional significance of regional distribution of hypophyseal portal system; 9) mechanisms involved in selective uptake of labeled hormones; 10) hypothalamic lesions in species with spontaneous ovulation and active luteal function; 11) direct effect of gonadal hormones on single hypothalamic neurones studied with combination of microinjection and unit recording devices; 12) studies of the possibility of a direct feedback of gonadotropic hormones on the hypothalamus; 13) studies of the receptor mechanisms involved in neuroendocrine reflexes; 14) wider exploration of brain structures, with regard to feedback action of gonadal hormones; 15) studies of pineal function; 16) further investigation of a possible role of the peripheral autonomic pathways in reproductive processes; and 17) research on the application of tissue culture techniques for studying problems of the origin and metabolic effects of neurohormonal mediators and the biochemcial and morphological changes induced by sex hormones.
International Family Planning Perspectives. 1992 Jun; 18(2):75-7.The main points of a study from the WHO Special Program of Research, Development and Research and Training in Human Reproduction on menstrual bleeding patterns and contraceptive use are presented. 1875 users of oral contraceptives, 1822 users of monthly injectables, 546 users of vaginal rings, and 1109 depot-medroxyprogesterone acetate (DMPA) users kept diaries of full bleeding and days of spotting during the 1st year a method was started. This information was compared with data from the 1930s and 1960s on bleeding patterns among nonusers of contraceptive methods. Monthly data were excluded in which pregnancy occurred of following a pregnancy, and when there were menstrual disorders or gynecological surgery. Data were then limited to women aged 18-34 years which left 3893 woman years of menstrual cycles. The results revealed that women who used hormonal contraceptives such as the vaginal ring or monthly injectables tended to have shorter periods of menstrual bleeding and more regular predictable periods than women on longterm injectables. Most women have variable bleeding patterns during the year, even when not using hormonal methods. Nonusers, pill users, and vaginal ring users had a median of just more than 3 bleeding or spotting day episodes during a 90-day period vs. 3 days among injectable users and <2 days for DMPA users. However, when the average duration of bleeding or spotting episodes was examined, the median was 4 days for pill users, 5 days for vaginal ring users, and 6 days for DMPA users. Menstrual cycle average length was lowest at 26 days for vaginal ring users, 28 days for nonusers, 29 days for injectable users, and 36 days for DMPA users. The median value for difference between the longest and the shortest cycle within 12 months was around 10 days for nonusers and pill users and 24 days for injectable or vaginal ring users vs. 55 days for DMPA users. The median for the longest episode of bleeding or spotting was 5 days for pill users, 7 days among nonusers, monthly injectable users, or vaginal ring users, and 12 days among DMPA users, of which 25% bled for at least 21 days and 1 in 29 bled for 55 days or more. The shortest bleeding-free intervals was the median for vaginal ring users at 21 days, and longest for DMPA users at 27 days. Other methods were similar to the intervals for the vaginal ring. 25% of DMPA users had a minimum bleeding-free interval of only 2 days, and 25% had an interval of at least 20 days. The myth is debunked that normal women have normal and regular cycles of 25-35 days.
Multinational comparative clinical evaluation of two long-acting injectable contraceptive steroids: norethisterone oenanthate and medroxyprogesterone acetate: 2. bleeding patterns and side effects.
Contraception. 1978 May; 17(5):395-406.A WHO sponsored comparative trail (9 centers) studied the bleeding patterns and side effects experienced by 1678 women using injectable (every 12 weeks) norethisterone enanthate (NOR) and depot-medroxyprogesterone (DMPA). 388.8 women-years of menstrual experience with NOR and 372.5 with DMPA were studied. The percentage of women with total amenorrhea with DMPA was significantly higher than with NOR for all injection intervals. The porportion of women with total amenorrhea increased significantly over time with both drugs (chi-square=33.9 for NOR and 73.4 for DMPA; P < .001). After 1 year, 35% of DMPA and 8.6% of NOR users had total amenorrhea. With NOR, the cycle length distribution changed markedly over time, with the percentage of short cycles under 25 days diminishing as the percentage of long cycles in excess of 46 days increased. In contrast, DMPA held cycle length patterns more or less constant. Length of bleeding and spotting episodes were significantly greater with DMPA. The mean number of bleeding/spotting days decreased over time with both drugs; the difference from the 1st to 4th injection was statistically significant (P < .001). Though the overwhelming majority of women experienced abnormal cycles with both drugs, the percentage of normal cycles remained fairly constant during consecutive intervals. Headache was the most frequently reported complaint: 10.7% of DMPA and 6.9% of NOR users. Other nonmenstrual side effects were reported with similar frequencies in both groups.