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The question of differential effects on bone density by two different types of progestogen-only methods for contraception in premenopausal women was addressed. Data from a prospective randomized clinical trial among 22 premenopausal women, age 32.6 (range 20-45 years), who were randomly assigned to either of two treatments with continuous progestogens for contraception were analyzed; depot-medroxyprogesterone acetate (DMPA) or continuous levonorgestrel treatment with subdermal implants (Norplant), respectively. Forearm bone density (BMDprox) increased with 2.94% (p = 0.006) in women who were prescribed levonorgestrel, which was in contrast to stable values in those prescribed depot-medroxy-progesterone acetate; group difference at 6 months for BMDprox 3.4% (95% CI 1.3, 5.5; p = 0.025) and BMDdist 4.1% (95% CI - 1.3, 9.6; p = 0.077). The changes in bone density were consistent with the changes in biochemical indices for bone metabolism; DMPA users showed signs of increased bone turnover and users of levonorgestrel showed increased bone formation with increased levels of both alkaline phosphatase (p = 0.004) and osteocalcin (p = 0.007). The findings suggest an increase in bone density during treatment with levonorgestrel and stable values during short-term administration of DMPA, in standard clinical doses for contraception.

Two groups, each composed of 20 women, who used depomedroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) injectable contraceptives were investigated for changes in 75-g OGTT and in the fasting and two-hour post oral glucose load (2-hours) levels of serum insulin, growth hormone, glucagon, cortisol and blood pyruvate. Samples were taken before and 3, 6 and 12 months after use of injectables. DMPA and NET-EN caused significant changes in mean blood glucose and pyruvate and in mean serum insulin, growth hormone and glucagon, but not in mean fasting cortisol. Changes with NET-EN started after 3 months, became maximal after 6 months and reverted to normal after 12 months of use, due to more frequent administration during the first 6 months of use (every 60 +/- 5 days) and to more spacing of the injections (every 84 +/- 5 days) after that. Changes with DMPA started after 3 months, and increased with the duration of use to become maximal after 12 months. Maximal changes were similar with DMPA and NET-EN and consisted of: a significant increase in fasting blood glucose and pyruvate and serum insulin; a significant increase in 2-hour blood glucose and pyruvate, serum insulin, growth hormone and glucagon. Although significant changes in blood glucose levels occurred with both DMPA and NET-EN, yet they did not reach the lower cut-off levels for impaired glucose tolerance in any user. With the same spacing of injections, i.e. every 84 +/- 5 days for NET-EN and every 90 +/- 5 days for DMPA, the effects on various parameters studied were less with NET-EN.

The short-term (3 months) and long-term (15 months) effect of DMPA contraception on various coagulation parameters (predictive of thrombosis) and on serum lipids (predictive of atherosclerosis) were prospectively studied in 30 Egyptian women, compared to their pretreatment levels. There were no significant changes in all the coagulation parameters studied after 3 months, and there was only a significant reduction in antithrombin III (AT III) level after 15 months (p less than 0.01). Concerning serum lipids, after 3 months, there were no significant changes in total lipids (TL), total cholesterol (TC) and triglycerides (Tg), while there was a significant decrease in high density lipoprotein cholesterol (HDL-C) (p less than 0.001), and a significant increase in low density lipoprotein cholesterol (LDL-C) (p less than 0.01). After 15 months there was a significant increase in TL, TC and LDL-C (p less than 0.001) and a significant decrease in HDL-C (p less than 0.001). Lipoprotein electrophoresis showed no significant change in pre-beta-lipoprotein percent, a significant decrease in alpha-lipoprotein percent and a significant increase in beta-lipoprotein percent after 3 and 15 months (p less than 0.001). Beta-lipoprotein band increased in 50% of DMPA users after 3 months and in 90% after 15 months and the type of hyperlipoproteinaemia was IIa. All calculated atherogenic indices showed significant changes (p less than 0.001) after 3 and 15 months of DMPA use. There was no significant correlation between AT III changes and changes in serum lipids. The study suggests no risk of thrombosis after 3 and 15 months of DMPA use. However, the risk of atherosclerosis appears to be possible as there were significant changes in serum lipids.

Gonadotrophin-releasing hormone agonists (GnRHAs) were investigated as contraceptive agents from the late 1970's to the mid-1980's. They were abandoned as they appeared to offer no advantage over conventional combination-type oral contraceptives (COCs). This conclusion appears to be incorrect. We propose here a contraceptive regimen of a depot formulation of a GnRHA plus add-back estrogen and intermittent progestogen. The dose of add-back sex-steroids is substantially less than that in COCs; this reduction in sex-steroids should lead to a major reduction in lifetime breast cancer occurrence.

To assess the effects of depot-medroxyprogesterone acetate (DMPA) upon serum lipids and lipoproteins, a comparative study in chronic users and new acceptors was undertaken. Two groups of women of reproductive age were included in the study; group I (n = 8) was formed by new acceptors whereas, group II (n = 14) constituted DMPA users of more than five continuous years (7.0 + 2.1 years). Blood samples were taken on the day of injection and 15, 29, 57 and 92 days after the i.m. administration of 150 mg of DMPA for the measurement of total triglycerides (TG), cholesterol (CHOL) and phospholipids (PHL). In addition, the TG and CHOL content in the very low density (VLDL), low density (LDL) and high density (HDL) lipoprotein fractions obtained by ultracentrifugation were also determined. The results demonstrated a moderate increase in the serum total TG concentrations at the expense of the VLDL fraction in the group of chronic DMPA users. In both groups, the administration of DMPA induced a moderate, though not significant, decrease in total CHOL and HDL-chol, an effect that was noticed at the end of the treatment interval; the serum LDL-chol content remained unchanged. In addition, a decrease in the total serum phospholipids content was noticed after DMPA injection in both groups, which resembled the fluctuations observed in the luteal phase of normal ovulating women. The overall data indicate that acute and/or chronic DMPA administration at the dose currently employed for contraception does not induce major abnormalities in lipoproteins in serum.

A comparative pharmacological pilot study of the monthly injectable contraceptive CycloProvera was carried out in 11 women in four centres. There were no significant differences in the results between the centres except that the injection-bleeding interval appeared to be shorter in Swedish women than in those in Havana and Mexico. Medroxyprogesterone acetate was detectable in blood for 28 to 62 days after injection of CycloProvera and although follicular activity returned in less than 28 days after injection in many of the women, corpus luteum function was suppressed for at least seven weeks in all women. Most of the women retained a regular menstrual pattern; six of 33 cycles were amenorrhoeic. There was no significant change in any of the biochemical and haematological analyses.

Proteins (total, albumin, globulin and their subfractions), carbohydrate (intravenous glucose tolerance test), lipids (serum cholesterol, triglycerides and phospholipids), and liver function tests (alkaline phosphatase, lactic dehydrogenase and aspartate aminotransferase activities in the serum, bromsulphathalein retention test and serum bilirubin) were studied in 12 non-lactating healthy Thai subjects before, and subsequently at 3 weeks and 3, 6, 9 and 12 months after the initiation of treatment with injectable medroxyprogesterone acetate (150 mg I.M. every 90 days). Serum protein and lipid levels, and the results of liver function and I.V. glucose tolerance tests, remained unchanged in all subjects throughout the one-year study period. However, a significant and persistent increased insulin level was noted in all subjects, after initiation of the hormone treatment, during the first thirty minutes of intravenous glucose load. It is concluded that injectable medroxyprogesterone acetate used as a contraceptive agent does not interfere with glucose tolerance, lipid and protein metabolism, and that the liver function remains normal during its administration.

Menstrual diary records were obtained from women using either a natural method of contraception, a combined or progestogen-only oral contraceptive, a vaginal ring, or a long-acting injectable (DMPA). Within each method group, multiple regression analysis was used to examine the relationships between the subjects' bleeding patterns and their age, age at menarche, ponderal index, obstetric and contraceptive history and ethnic origin. The influence of ethnic origin was described in the preceding paper. Among combined pill users, increasing age was associated with more frequent spotting episodes. In both the untreated and combined pill groups, women with a higher ponderal index had less variable bleeding-free intervals; in the vaginal ring and DMPA groups, the more obese women had shorter bleeding/spotting episodes and longer bleeding-free intervals. Among combined oral contraceptive users, the most influential variable was the time since the end of the woman's last pregnancy: subjects who had been more recently pregnant had longer, less predictable episodes and shorter intervals. Previous oral contraceptive use was associated with more predictable bleeding patterns among women currently using either type of oral pill. In the vaginal ring and DMPA groups, subjects whose last pregnancy had ended in abortion had more bleeding/spotting days and episodes than those who had had a live birth. As reported previously, bleeding patterns were more closely related to the woman's geographical region of residence than to any other factor. The associations found with other individual characteristics were often inconsistent or difficult to interpret. A number of variables which could potentially influence menstrual bleeding patterns, such as nutritional status, were not measured and therefore could not be included in the analysis. However, contraceptive method and ethnic origin may be predominant influences, overriding any other factor.

Several recent reports have documented a lower incidence of pelvic inflammatory disease (PID) among oral contraceptive users. The interpretation of this observation is difficult because the action of the contraceptive hormones may be directly by action on a specific host cell-parasite relationship, or indirectly via their action on other systems. In the present study we investigated the susceptibility of cultured human epithelial cells of the endometrium to infection by chlamydia and the influence of contraceptive steroids (ethinyl estradiol, mestranol and medroxyprogesterone acetate) upon replication of chlamydia in these cells. Forty-eight hours post-infection, elementary and reticulate bodies were observed in vacuoles of the infected endometrial cells by electron microscopy. Treatment of chlamydial-infected cells with contraceptive steroids in three different concentrations (10(-5)M, 10(-6)M and 10(-7)M) resulted in no effect on chlamydial replication, as examined by one-step growth curve. These results indicate that contraceptive hormones do not prevent chlamydial infection by direct effect on the replication of the agent.

The effect of a single dose of 150 mg of depo-medroxyprogesterone acetate (DMPA) on pituitary, ovarian and endometrial function was assessed in relation to the peripheral levels of the compound in 8 women. The levels of medroxyprogesterone acetate (MPA), follitropin (FSH), lutropin (LH), prolactin, estradiol (E2) and progesterone ( Prog .) were measured 3 times a week during a pretreatment (control) cycle and then daily during postinjection weeks 14-17, 22-25 and 30-33. An endometrial biopsy specimen was obtained during postinjection weeks 17, 25 and 33. In three out of 8 subjects the daily hormone assays carried out during postinjection weeks 30-33 indicated anovulatory periods; in these subjects peripheral blood was drawn daily during postinjection weeks 46-49 and a fourth endometrial biopsy was taken during week 49.

A long-term follow-up study compared development and health of 128 breast-fed children whose mothers had received depot-medroxyprogesterone acetate (depot-MPA) while lactating and 142 control children whose mothers had used mechanical contraceptives or no contraceptives or had undergone sterilization. The children, who were approximately 4-1/2 years old at follow-up, showed no ill effects on their growth and development and health status from exposure to depot-MPA. Depot-MPA-treated mothers lactated significantly longer than controls and also had greater parity than controls. These factors apparently contributed to a difference in weight at follow-up. Compared with the Sempe-Pedron standard, more of the depot-MPA group were underweight and more controls were overweight.

Records of the occurrence of vaginal bleeding were obtained from women using either a natural method of contraception or one of four types of hormonal contraceptive. The relationships between their bleeding patterns and a number of demographic variables were examined, with the aim of identifying subgroups of women who, if they used a particular hormonal method of contraception, would be likely to suffer more or less disruption to their bleeding pattern than the 'norm'. Within contraceptive method, bleeding patterns were more closely related to the women's geographical region of residence than to any other factor. Some of the differences between regions were consistent across contraceptive methods. European women tended to have more bleeding/spotting days than women in other regions; Latin American women had relatively short episodes and long bleeding-free intervals, whether they were using the ovulation method, combined pills or a vaginal ring. Other differences were method-specific. Women using combined pills in India or Pakistan had fewer spotting episodes than women using the same method elsewhere; those using progestogen-only pills had more. Regional variations in bleeding patterns were particularly marked among women using DMPA, and increased over time: by their fourth injection interval, 25% of European women had amenorrhea, as compared with 72% of subjects in North Africa. These findings need to be confirmed by carefully controlled studies of menstrual bleeding patterns and their acceptability in various ethnic groups. The results would be valuable in counselling new contraceptive acceptors, and could eventually guide the choice of methods for introduction into national family planning programmes.

A rapid method for the determination of DHT (5 alpha-dihydrotestosterone) in serum was established, utilizing potassium permanganate as an oxidising agent to convert the double bond at position 4-5 of testosterone to dihydroxy alcohols. DHT was then extracted with diethyl ether and measured directly using radioimmunoassay technique. The precision of the assay was determined at three levels of DHT added into pooled serum and found to be 4.4-5.1% for between assay percentage coefficient of variation. The sensitivity of the standard curve was found to be 4.2 pg/0.5 ml sample. The accuracy was determined in pooled serum with added standard DHT in the range of 80-800 pg. The percentage recovery of the assay was found to be 92.93-98.35%. The antisera used for DHT assay exhibited no significant cross-reaction with various steroids tested except testosterone which showed a 91.3% cross-reaction. The method was applied to measure the level of DHT in serum of Thai males receiving medroxyprogesterone acetate (MPA) as an oral contraceptive. Twenty-five subjects were divided into 5 groups. Group 1 received an oral placebo with monthly sesame oil injection. Groups 2, 3 and 4 received 5 mg, 10 mg and 20 mg MPA, respectively, with the addition of monthly injection of 250 mg testosterone enanthate (TE). Group 5 received 20 mg MPA daily with the addition of monthly injection of 500 mg TE. Blood specimens were obtained monthly. The first 4 months were used as a control period. After the 4-month period, each subject received treatment as mentioned above for 6 months, then follow-up study was resumed for another 6 months. The results revealed that subjects receiving 20 mg MPA with the addition of 250 mg TE showed a significant decrease of DHT levels (p less than 0.001).

A male contraceptive trial was undertaken in 23 men using a combination of oral medroxyprogesterone acetate (MPA) and oral methyltestosterone (MeT). The men were divided into four groups according to varying drug dosages and were followed for 15 months (control - 3 months, treatment - 6 months, follow-up - 6 months). The parameters assessed included sperm count and motility, serum gonadotropins and sex steroids, and several biochemical and hematological tests. A questionnaire dealing with side-effects and changes in sexual function was administered intermittently. Although sperm count was suppressed (most dramatically at the highest drug doses, MPA 20mg,MeT 20mg), it was not suppressed to infertile levels. Sperm motility was unaltered; LH was modestly suppressed, FSH was not suppressed; testosterone was suppressed even at low doses; dihydrotestosterone responses were inconsistent. No significant biochemical abnormalities or side-effects occurred although some men experienced mild transient acne, gynecomastia and decreased testicular size. We conclude that in the doses used in this trial, the combination of MPA and MeT is not effective for male contraceptive, purposes and that higher doses may induce severe and undesirable side-effects.

Histological changes were studied in the ovary and uterus of rats receiving different doses of Depo-Provera (DMPA) and Noristerat (NET-EN) for varying duration. The effect of DMPA on ovarian and uterine tissues was strongly progestational. The whole morphological alteration in the ovary after DMPA therapy appeared to be the atresia of the follicular apparatus with degeneration of the growing follicles. Uterine histology reflected that endometrial tissues gradually became inactive and with prolonged treatment at high doses, atrophy of the endometrium was noted. In NET-EN-treated rats, absence of mature follicles and recent corpora lutea reflected the blockade of ovulation. There was no extreme atrophy of the ovary or endometrium as found with DMPA treatment. With higher doses of NET-EN, endometrial growth was arrested.

A fasting plasma lipid profile investigation was undertaken in 63 women who were on contraception with the 3-monthly intramuscular depo-provera injection for periods ranging from 3 to 30 months. Fifty nulliparous women, with no previous history of contraceptive therapy, matched for age, parity, height and socio-economic status, served as controls. History of clinico-physiological side effects was recorded. The results show reduced levels of fasting plasma cholesterol in patients on depo-provera compared to the control group but there was no significant change in fasting plasma phospholipid levels. Contrary to expectations, the patients on depo-provera had higher fasting plasma triglyceride levels than controls. Excessive weight gain and irregular heavy bleeding represent major reasons for withdrawal from depo-provera therapy. The findings suggest that the alterations in the plasma lipid profile, body weight and side effects experienced by women on depo-provera may be inversely related to the duration of effective therapy.

From June 1974 to June 1976, 665 women who had given birth to full-term infants and who were willing to nurse the infant were admitted to this study. At three to six weeks postpartum, subjects chose which of four study groups to join. One-hundred-forty-three mothers chose Group I, exclusive lactation with no contraception; 109 chose Group II, lactation and intrauterine contraception (IUD); 228 chose Group III, lactation and an intramuscular injection of 150 mg medroxyprogesterone acetate (Depo-Provera Sterile Aqueous Suspension, DMPA) given every three months; and 185 chose Group IV, lactation and one tablet of 0.6 mg Clogestone Acetate given daily. Mother and child were examined monthly until the child's spontaneous weaning, the mother's dropout, or the study's close in 1979. Mothers from Group I (exclusive lactation) were dropped from study when they requested and were prescribed a contraceptive. During the first six months of study, the percent of mothers who dropped out of Groups I, II, III, and IV for personal or medical reasons was 28.0, 16.5, 11.4, and 27.1, respectively. Pregnancies began to occur in the sixth month postpartum. Overall, pregnancies occurred in 6% of mothers in exclusive lactation, 3% of mothers protected by an IUD, and 8% of mothers protected by Clogestone. No pregnancies occurred in the 228 women receiving DMPA. Some mothers in the Clogestone or DMPA groups were still breast-feeding their children two or three times a day at the study's close, at which time the child was three or more years of age. No ill effects were observed in growth and development of these children during the study. The DMPA group had the most mothers who were breast-feeding for more than 20 months.

A potential male contraceptive approach was evaluated in clinical trials involving monthly injections of depot medroxyprogesterone acetate and either subdermal implants of testosterone propionate or monthly injections of testosterone enanthate. Pregnancies occurred in partners of 9 men with recent sperm counts of 10 million/ml or below. In 5 of the 9 instances, the sperm counts were less than 1 million/ml. It appears that male contraceptive methods involving spermatogenic suppression may require attainment and maintenance of azoospermia. The pregnancy rate cannot be calculated, because the extent of other contraceptive use is uncertain. There were no spontaneous abortions. 6 pregnancies were carried to term, and all progeny were normal, based on physical examination at birth or 3 months after birth.

Final results are presented from a two-year WHO multinational comparative trial of three regimens: depot-medroxyprogesterone acetate (DMPA) given at 90-day intervals, norethisterone enanthate (NET-EN) given at 60-day intervals for the entire study period (NET-EN (60-day)), and NET-EN given at 60-day intervals for six months and thereafter at 84-day intervals (NET-EN (84-day)). 1587 DMPA subjects were observed for 20,550 woman-months, 789 NET-EN (60-day) subjects were observed for 10,361 woman-months, and 796 NET-EN (84-day) subjects were observed for 10,331 woman-months. This clinical trial represents the largest clinical trial undertaken on injectable contraceptives. After two years, the pregnancy rate with NET-EN (84-day) was 1.4 (+/- 0.6 S.E.) per 100 women, as compared with the two-year rates of 0.4 (+/- 0.3 S.E.) per 100 women observed with DMPA and 0.4 (+/- 0.2 S.E.) with NET-EN (60-day). Both discontinuation rates for amenorrhea and the prevalence of amenorrhea lasting more than 90 days were significantly higher with DMPA than with either NET-EN regimen. Terminations for bleeding problems were similar with the three treatments, despite a better cyclic pattern for the first six months with the NET-EN regimens. The three treatments were comparable with respect to discontinuation rates for other medical or personal reasons, and for all reasons combined. For family planning programs, NET-EN (60-day) has the advantage of low pregnancy rates compared to NET-EN (84-day), and a schedule of administration that does not change. Both NET-EN regimens produce less amenorrhea than DMPA. However, the NET-EN (60-day) regimen has the logistic and economic disadvantage of requiring more frequent injections. All three injectable regimens compare favourably with oral contraceptives in terms of pregnancy and total continuation rates observed in clinical trial settings.

The effect of the two long-acting progestational contraceptive injection, depot-medroxyprogesterone acetate (DMPA) and norethisterone onenathate (NET-OEN), on blood phospholipid fractions were studied in eighteen women. The post-injection results showed a significant increase in total serum phospholipids, serum lecithin and serum cephalins. Serum lysolecithin was significantly decreased while serum sphingomyelin showed no significant change. The mechanisms responsible for these phospholipid changes remain somewhat unclear. However deranged liver function may share in its explanation.

To evaluate the influence of sex steroids on immunity in 87 women on hormonal contraceptives, sensitization tests were performed with the contact allergen, 2,4-dinitrochlorobenzene (DNCB). Forty-five women were taking oral contraceptives of combined oestrogen/progestogen of the same brand (low oestrogenic and middle range progestogenic activity); 27 had received intramuscular injections of medroxyprogesterone acetate and 15 women were using a sequential pill. The results were compared with those of 44 women not taking contraceptive steroids and matched for age. In women on the combined pill and those who had received intramuscular progesterone, the mean DNCB reactivity was significantly increased (0.02 less than p less than 0.05 and 0.001 less than p less than 0.01, respectively), whereas women using a sequential pill proved to show a decreased skin reactivity in the oestrogenic phase of this pill. (p = 0.05). The changes observed proved to be specific, since no statistically significant differences in overall skin reactivity to irritants between the four groups of women could be observed. The clinical implications of these results have been considered.

Eight normally menstruating women received Cycloprovera (25 mg medroxyprogesterone acetate with 5 mg estradiol cypionate) and seven other volunteers received HRP-102 (50 mg norethisterone enanthate with 5 mg estradiol valerate) injections at 30-day intervals for three consecutive months. The peripheral plasma levels of estradiol (E2), progesterone (PROG), medroxyprogesterone acetate (MPA) and norethisterone (NET) were measured in the luteal phase of a pretreatment cycle, during the third treatment month and during a subsequent recovery period of 60 days. Blood samples were drawn three times a week (Mondays, Wednesdays and Fridays) and endometrial biopsies were taken on day 20 to 26 of the pretreatment cycle, 20 to 24 days after the last injection and 20 to 24 days after the first normal menstrual-like bleeding during the recovery period. The (geometric) mean maximum level of MPA was 2.9 (2.4-3.7) nmol/1 and that of NET 10.1 (6.4-15.8) nmol/l. Thirty days after the last injection, the MPA level was 0.72 (0.46-1.1) nmol/l and that of NET 1.7 (1.2-2.3) nmol/l. The maximum level of exogenous E2 was 890 (700-1130) pmol/l after Cycloprovera and 1570 (870-2820) pmol/l after HRP-102 administration. Forty-nine and 41 days, respectively, after the last injection, a broad (endogenous) E2 peak was observed in all subjects, which was not followed by an ovulatory rise in PROG levels. The first ovulatory rise in PROG occurred between 71 and 90 days after the last Cycloprovera and 59 to 87 days after the last HRP-102 injection. One subject in each of the two groups failed to ovulate during the 90-day post injection period. Dating and morphometric analysis of the endometrial biopsy specimens obtained 20 to 24 days after the last injection revealed that the suppressive effect of Cycloprovera was stronger than that of HRP-102. Each injection of both formulations was followed by a bleeding-free period of approximately two weeks. The percentage of days with bleeding and spotting was 24% for Cycloprovera and 29% for HRP-102. It is concluded, that both monthly injectables inhibit follicle maturation for some 30 days and ovulation and corpus luteum formation for some 60 days, providing thus a considerable margin of safety in terms of the expected duration of contraceptive protection.

Hormonal substances for male fertility regulation administered orally or by injection are currently undergoing clinical evaluation. These trials, sponsored by the World Health Organization, provide unique opportunities for intensive study of the acceptability of such an approach to fertility regulation, and of these drugs in particular. The research employs repeated interviews over a 15-month period and is conducted by social scientists collaborating with biomedical scientists at each of seven sites (Bangkok, Hong Kong, London, Mexico City, Santiago, Seoul, and Toronto). The focus is upon gauging male user's evaluations of hormonal methods (several androgen/gestagen combinations as well as cyproterone acetate) relative to their evaluations of other male methods they know about or have experienced. Of particular importance is to determine whether the hormonal methods modify or interfere with sexual desire, feelings, and behavior. The research is also assessing specific ways in which various perceived properties of fertility regulating methods relate to their acceptability in different socio-cultural settings.

Doses of DepoProvera of 25, 50, 100 and 150mg were administered to four groups of women. The mean time for the return of follicular and luteal activity increased with increasing dose of DepoProvera. Luteal activity was suppressed for a longer period than follicular activity. None of the women receiving the two higher doses of DepoProvera showed a return of luteal function within 100 days of injection. The period for which medroxyprogesterone acetate (MPA) was detectable in serum increased with increasing dose but the values for the 100 and 150mg doses were not significantly different. There was a significant correlation between the concentration of MPA in blood and the return of follicular and luteal function. It is suggested that in the population studied, 100mg DepoProvera would be as effective as the usual 150mg dose and that injection of 50mg DepoProvera would provide a contraceptive effect for two months. The dose of MPA in the monthly injectable CycloProvera could be substantially reduced without loss of effectiveness.

In an attempt to assess the effect of depot-medroxyprogesterone acetate (DMPA) on adrenal function, to peripheral levels of a variety of steroids were estimated after dexamethasone suppression and subsequent ACTH stimulation in 5 subjects. The steroid responses observed 16 and 54 days after a single injection of 150 mg of DMPA were compared with those obtained in the same women before DMPA treatment or with those found at different phases of the cycle in another group of 6 normally menstruating women. The levels of cortisol, pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenedione and dihydrotestosterone were significantly suppressed by dexamethasone and stimulated by ACTH in all phases of the cycle, and before and after DMPA administration. The extent of suppression or stimulation (expressed as a percentage) was different in case of different steroids, but was rather constant with regard to the same steroid. Hence, the functional capacity of the adrenal as reflected by the levels of these steroids. Dexamethasone administration did not exert any influence on the levels of progesterone and 17-hydroxyprogesterone during the different phases of the cycle; however, ACTH administration increased the levels of these two steroids in the follicular phase and also after DMPA treatment. The levels of estradiol and lutropin were not influenced by dexamethasone or ACTH at any of the occasions studied. It is concluded that the functional capacity of the adrenal cortex is constant during the various cycle phases and is not affected by the administration of a single dose of 150 mg of DMPA.

Depo-medroxyprogesterone acetate (DMPA) in the conventional dose of 150 mg, was administered intramuscularly to 49 healthy, already sterilized, Thai women on cycle day 5 (13 subjects), day 7 (12 subjects), day 9 (13 subjects) and day 11 (11 subjects) of normal menstrual cycles. Serum progesterone levels were then monitored in order to ascertain the latest follicular phase day in the cycle (up to day 11) when ovulation would be inhibited in the first month after injection. Among the 25 subjects who received DMPA on day 5 and 7, no longitudinal serum progesterone level rises indicative of ovulation were detected. When DMPA was given on day 9 and 11, 2 out of 13 subjects (15.39%) and 3 out of 11 subjects (27.28%), respectively, had serum progesterone levels characteristic of ovulation. It is concluded that the initial cycle's ovulation can also be inhibited when DMPA is administered on day 7 of that cycle. However, DMPA administered on day 9 and 11 failed to inhibit ovulation of that cycle in some of the subjects.

Twenty-three men who participated in a 15-month clinical trial to assess the potential effectiveness of using a combination of varying doses of medroxyprogesterone acetate (MPA) and methyltestosterone (MT) as a male contraceptive agent, completed a "sexual problem checklist" every two weeks. The study was divided into three phases: pre-treatment (3 months), treatment (6 months), post-treatment (6 months). The questionnaire evaluated changes in various aspects of sexual behaviour and sexual perception and explored whether the treatment influenced any of the parameters considered. The results indicated a small, but significant, decrease in subjective assessment of sexual drive. This was not, however, accompanied by a change in sexual behaviour, in that subjects experienced the same number of erections, ejaculations and frequency of intercourse. It is concluded that the combination of MPA and MT in the doses used may produce a slight decrease in subjective assessment of sexual drive, but no change in actual sexual behaviour.

One-hundred-and-thirty normally menstruating females were subgrouped equally and enrolled from the family planning clinic to study the clinical performance of the monthly injectable contraceptives medroxyprogesterone acetate 25 mg + estradiol cypionate 5 mg (Cycloprovera) and norethisterone enanthate 50 mg + estradiol valerate 5 mg (HRP-102) and their effects on some metabolic parameters. The contraceptive efficacy after 6 months of use for both drugs was 100%. No change in menstrual pattern occurred in 74% of Cycloprovera users and 67.3% of HRP-102 users. A statistically significant decrease (P less than 0.01) occurred in HDL-cholesterol and total serum protein values and a statistically significant increase (P less than 0.01) was observed in hematocrit value of Cycloprovera users only. Body weight and blood pressure values after 6 months of drug use showed no statistically significant changes in both groups. Also, no statistically significant changes were noticed in both groups for hemoglobin, post-prandial blood glucose, cholesterol, A/G ratio, SGPT and SGPT values following 6 months of injectable contraceptive use. None of the injectable users developed cervical dysplastic changes cytologically.

WHO conducted a three-centre study in Hungary and Thailand to evaluate the effects of hormonal contraception on lactation and infant growth. Women choosing oral contraceptives were randomly assigned to a combined oral contraceptive containing 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel (N = 86) or a progestin-only preparation containing 75 micrograms dl-norgestrel (N = 85). Identical packaging and treatment schedules allowed double-blind observation. One-hundred-and-eleven women using no contraception or non-hormonal methods acted as controls. In the two Thai centres 59 women using depot-medroxyprogesterone acetate formed an additional comparison group. All subjects were healthy women with normal deliveries, whose infants had normal birth weights and satisfactory growth in the neonatal period. Breast milk volume was determined by pump expression using standardized procedures. Information was obtained on nursing frequency and supplementation, infant growth and morbidity. Pretreatment observations at 6 weeks post-partum were used as a baseline, and subjects were followed-up at 9, 12, 16, 20 and 24 weeks post-partum. Women using combined oral contraceptives had a decline in milk volume within 6 weeks of initiating treatment, whereas no significant decrease was observed in the other treatment groups. After 18 weeks of treatment, combined oral contraceptive users experienced a 41.9% decline in milk volume, compared to 12.0% with progestin-only minipills and 6.1% in the non-hormonal controls. The prevalence of complementary feeding and withdrawals due to inadequate milk supply were comparable in the four treatment groups. However, data were not available on the daily amounts of complementary feeds. There were no significant differences in growth of infants between treatment groups. Thus, women may have compensated for declines in milk volume by more supplementary feeding or by more prolonged and intense suckling episodes. We conclude that 30 micrograms estrogen-containing combined oral contraceptives impair milk secretion, but in the selected healthy group of mothers and children studied with the prevailing level of supplementary feeding, this did not adversely affect infant growth.

The metabolic effects of an injectable contraceptive, Depo-provera (medroxyprogesterone acetate), an oral contraceptive pill containing 50 micrograms ethinyl estradiol and 500 micrograms norgestrel and a control group (not on contraceptives) were compared in 3 groups, each comprising 32 women. The subjects were matched for race, age and parity. Mean duration of treatment was 41.7 +/- 18.3 months for Depo-provera and 59.6 +/- 29.0 months for the pill group. Glucose tolerance was impaired in both treatment groups. The combination pill showed more changes in both glucose tolerance and insulin response. Lipid levels remained unchanged in both treatment groups.

The effect of one year's continual use of medroxyprogesterone acetate as an injectable contraceptive (150 mg I.M. every 90 days) on vitamin (A, B-carotene, E, B-1, B-2, B-6, oral tryptophan load test, folate and B-12) and trace mineral metabolism (Na, K, Ca, Mg, Cu, Zn and phosphorus) were assessed before and at the 3rd week, 3rd, 6th, 9th and 12th months after initiation of daily treatment with a vitamin-mineral supplement, in 12 non-lactating helathy Thai women. Neither vitamin nor trace mineral metabolism changed significantly as a result of treatment when compared to the pre-treatment control, suggesting that this form of hormonal contraceptive did not interfere with any of the parameters studied.

Adrenal function and its reserve capacity were studied in eighteen healthy non-lactating women who received depot-medroxyprogesterone acetate (DMPA: 9 subjects) and norethisterone enanthate (NET-EN: 9 subjects) as long-acting injectable contraceptives. Methodological assessments included: (i) morning fasting concentration of serum cortisol; (ii) diurnal variation of adrenal corticol activity as evidenced by cortisol concentration in serum samples taken at 0700 and 1600 hours; (iii) urinary free cortisol excretion; and (iv) cortisol response to insulin-induced hypoglycaemia. None of these assessments was significantly altered by contraceptive administration. This finding indicates that the subject's ability to release cortisol in response to a stressful situation, as well as to normal day-to-day activity, was not impaired by these contraceptive steroids.

Antibodies produced by the vaccine Pr-beta-hCG-TT in monkeys were effective in terminating pregnancy in baboons on passive administration. The animals returned to cyclicity soon after the onset of vaginal bleeding. Fertility was regained. Globulins from non-immunized control monkeys in amounts, volume and injection schedule similar to those employed for passive termination did not intercept pregnancy. The abortifacient action of anti-CG antibodies could be counteracted by administration of medroxyprogesterone acetate.