Effects of hormonal and nonhormonal contraceptives on lactation and incidence of pregnancy.

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.

Endometrial findings in postmenopausal women receiving long-term estrogen therapy.

An histological study of the endometrium of 43 postmenopausal women under the chronic effect of cyclically administered conjugated estrogens was performed. Four atypical hyperplasias and one adenocarcinoma in situ were found. The frequency of these findings is similar to the one found in a sample of the population consulting the gynecologic clinic of our Hospital that never received estrogen therapy.

Human lactational response to oral thyrotropin releasing hormone.

Several studies were designed to evaluate the effect of oral TRH on prolactin (PRL) secretion and mammary function in nursing women. Initially, efficacy was studied in nursing women following 5 mg TRH. PRL levels rose to a mean maximum of 46.3 ng/ml above baseline at 60 min. Plasma TSH also incresed from a mean baseline of 2.6 to 17.6 muU/ml at 180 min. No changes were observed following placebo. In order to observe the long term effects of oral TRH, two groups of women in full nursing were studied. Beginning on day 29 postpartum, either 5 mg TRH or placebo were taken twice daily for four weeks. No chronic elevations were observed in maternal PRL and TSH or in infant TSH before or after one month of either regimen. Milk composition expressed in terms of per cent protein and per cent fat did not differ between the groups. Weekly gonadotropin levels were also similar as were infant weight gain and growth. In a group of women with lactational insufficiency receiving 5-20 mg TRH twice daily for five days, basal PRL concentrations markedly increased. While changes in milk composition were not significant, fat percentages increased slightly and protein percentages declined. Breast engorgement and milk letdown increased and full nursing was restored. While the oral TRH used in fully nursing women had no demonstrable effect on mammary function, it may prove useful in those women with lactational insufficiency. Because two women developed iatrogenic hyperthyroidism following 40 mg oral TRH twice daily, care must be exercised in determining the dosage to be employed.

Effect of a long-acting contraceptive progestogen on lactation.

A prospective study was made on the duration of lactation in 406 mothers injected postpartum for contraception with medroxyprogesterone acetate (DMPA), 150 or 250-300 mg, IM, at 3- or 6-month intervals. Breast feedings up to 2 per day were recorded, and findings compared with those from 173 nontreated controls. Eighty percent of the DMPA group were nursing successfully at the sixth month and 42% at the 12th month postpartum. These figures are significant and compare favorably with the control group. No advantage was found in the administration of DMPA earlier than the second or third month after delivery. Amenorrhea persisted during lactation. No pathologic breast conditions were observed. The eventual mechanism of DMPA in galactopoiesis has yet to be clarified.

Significance of the secretion of human prolactin and gonadotropin for puerperal lactational infertility.

The causes of puerperal infertility in lactating women are poorly understood. The controlling centres may be either the hypothalamic-pituitary axis or the ovary (or both). We studied the secretory dynamics of prolactin and gonadotropins in healthy, normal, lactating and non-lactating women after administering either gonadoliberin to assess pituitary responsiveness or human menopausal gonadotropins to assess ovarian responsiveness during the puerperium. A reciprocal relationship was observed between the secretion of gonadotropins and the secretion of prolactin after the nipples of mothers who were breast-feeding had been stimulated for 30 min. The absence of a short-loop negative feedback control by prolactin for gonadotropin secretion was not confirmed because cyclic secretion of gonadotropin was not necessarily impaired by hyperprolactinaemia. Hyperprolactinaemia did, however, appear to impair the function of the corpus luteum in women suffering from non-puerperal galactorrhoea. We postulate a multifactorial mechanism for puerperal infertility based initially on the peripheral concentration of prolactin and gonadotropins and, in some poorly defined way, on the cerebral concentration of catecholamines.

Attempts to programme ovulation with exogenous oestrogens and LH-RH analogue.

An attempt was made to programme ovulation in women on a predetermined day of the menstrual cycle by treatment used to induce ovulation in anovulatory sterility. At laparotomy for elective sterilization the ovaries were observed to assess the occurrence of ruptured follicles and ovulation. Histological analysis of ovaries and endometrium was performed, and ova were recovered from some women. Several regimens were tested but ovulation seldom occurred as planned. Clomiphene citrate, human chorionic gonadotrophin (HCG), synthetic luteinizing hormone releasing hormone (LH-RH), and ethinyloestradiol were ineffective. Human menopausal gonadotrophin followed by HCG was more effective, but multiple ovulations occurred. When one single injection of a potent long-acting LH-RH analogue was given on day 13 of the cycle to 10 women pretreated with ethinyloestradiol signs of recent ovulation were observed on day 15 in seven and on day 16 in two.

Ovulation induction: ovarian response to human gonadotropins and synthetic gonadotropin-releasing hormone.

Human ovarian responses to FSH- and LH-releasing hormone (FSH/LH-RH) were observed at laparotomy and studies by histologic and histochemical examination of ovarian biopsy specimens. The responses were compared to those induced by human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) singly and together. The subjects were healthy, fertile, young women rendered anovulatory by injections of depomedroxyprogesterone acetate (DMPA) or depochlormadinone acetate (CA). Supplementary studies included measurement of urinary pregnanediol, examination of the cervix and vagina for estrogenic and progestational responses, and endometrial biopsy, Both HMG and HCG induced follicular growth and proliferation of granulosa and theca cells, but neither, when given alone, induced ovulation or corpus luteum formation. When given in conjunction they induced single or multiple ovulations and corpora lutea in 11 of 18 women treated. FSH/LH-RH CONSISTENTLY STIMULATED FOLLICULAR DEVELOPMENT AND INDUCED OVULATION IN 2 OF 16 WOMEN TREATED. Preovulatory mature follicles were found in 3 more. FSH/LH-RH may prove to be useful in the treatment of some cases of anovulatory sterility of hypothalamic origin.

Induction of ovulation with synthetic gonadotrophin-releasing hormone in women with constant anovulation induced by contraceptive steroids.

The ovarian response to stimulation with follicle-stimulating hormone/luteinizing hormone-releasing hormone (FSH/LH-RH) was studied in young, healthy, and fertile women with constant iatrogenic anovulation caused by depot medroxyprogesterone acetate or depot chlormadinone acetate injected for contraceptive purposes. Results were compared with those in unstimulated controls. The response was observed directly on the ovaries at laparotomy performed after treatment with FSH/LH-RH. A wedge biopsy provided ovarian tissue for histological and histochemical studies of steroid dehydrogenase activity. Treatment with FSH/LH-RH caused a trophic effect on the ovaries, with evidence of follicular development; ovulation occurred in two out of 16 treated women. Preovulatory mature follicles were found in three others.Clearly the FSH/LH-RH-induced release of FSH and LH caused follicular growth up to Graafian follicles, mature preovulatory follicles, and ovulation. Mitosis in granulosa and theca cells was also observed. A wide individual variation in gonadal response to hypothalamic FSH/LH-RH was evident, however. Nonetheless, our data support the possibility that treatment with FSH/LH-RH may prove valuable in patients with anovulatory sterility of hypothalamic origin.