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To investigate the mechanisms responsible for the postpartum suppression of reproductive function, LH and PRL levels were determined at 10-min intervals for 8 h in 10 lactating women, in 10 nonlactating women treated with bromocriptine, and in 5 nonpuerperal women. The lactating women were studied on postpartum day 7 (n = 5) or between days 28 and 35 (n = 5). All nonlactating women were studied on day 7. Five of them were treated with the opioid antagonist naltrexone to evaluate the role of endogenous opioids. By using a specific LH assay which does not cross-react with hCG, we were able to measure pulsatile LH secretion in the early puerperium for the first time. On day 7, LH levels were below the detection limit in both lactating and nonlactating women, hence no pulses could be detected. Chronic opioid blockade in bromocriptine-treated non-lactating women did not result in increased LH levels. Pulsatile LH secretion was present between days 28 and 35 of lactation, although pulse amplitude (P less than 0.05) and mean LH level (P less than 0.05) were lower than in nonpuerperal women. Mean LH in lactating women was negatively correlated with mean PRL (-0.87, P less than 0.05). Deconvolution analysis of the PRL responses to suckling revealed that PRL was secreted in distinct bursts, separated by intervals of secretory quiescence. Mean duration of PRL bursts was 40 +/- 4 min and the maximum secretory rate was reached around the end of suckling. We conclude that pulsatile LH secretion is completely suppressed during early lactation and partially suppressed during late lactation. Because the duration of suckling was similar, the relatively strong suppression during the early puerperium must be due to additional inhibitory factors. It has been suggested that endogenous opioids are involved in this process, but our results in puerperal women do not support this hypothesis.

Summary. Recently, long-acting injectable forms of bromocriptine have become available for the prevention of lactation. The first developed depot-form was very effective, but had the disadvantage of a slowly metabolized carrier. We investigated the pharmacokinetics, efficacy, tolerance and safety of 40 and 50 mg of a new rapidly eliminated depotform in 61 postpartum women. Bromocriptine rapidly increased after injection and prolactin was effectively suppressed during the studyperiod of 60 days. Overall efficacy was very good or good in 98% and no rebound lactation occurred. Sixteen women experienced side effects. Tolerance at the injection site was good and safety tests did not show abnormalities. There were no differences between the two dosages. We conclude that this new depot-bromocriptine is a safe, well tolerated and effective drug in the suppression of prolactin and the prevention of postpartum lactation.

The new nonergot dopamine agonist CV 205-502 appears to be a promising alternative in the treatment of hyperprolactinemia. Regarding the potential use of CV 205-502 in infertility practice, we studied the influence of CV 205-502 on the return of endocrine fertility parameters during the physiological hyperprolactinemia of the puerperium. The resumption of pituitary and ovarian activity in 18 CV 205-502 treated women was compared with that in 10 bromocriptine-treated women. LH was measured by a new specific assay, which does not cross-react with hCG. This assay was also used in a second part of the study in which the pituitary function of 10 breast-feeding women was investigated. Both dopamine agonists adequately suppressed PRL. Pituitary secretion returned in the second week and was initially characterized by a high FSH/LH ratio. There were no major differences between CV 205-502 and bromocriptine. Ovulations occurred from day 18 on. The PRL rebound at the end of treatment seemed to play a role in the ovulation process. An acute increase of PRL just before midcycle was able to prevent ovulation. Breastfeeding women showed a delayed return of pituitary secretion: after a hypogonadotropic period, FSH returned in the third week and was followed by a period with a high FSH/LH ratio and follicular inactivity.

Objective To investigate the role of inhibin in the human puerperium, by measuring serum levels of immunoreactive inhibin in both lactating and nonlactating women. Design Prospective, comparative, open study. Setting Department of obstetrics and gynecology of a university hospital. Patients Fourteen healthy women who delivered at term: seven lactating women and seven nonlactating women treated with the dopamine-agonist CV 205-502. Main Outcome Measures Serum immunoreactive inhibin, PRL, FSH, LH, E 2 , and P. Results All women showed a rapid decline of immunoreactive inhibin levels during the first postpartum days. Thereafter the pattern depended on the way of feeding. Nonlactating women, with their rapid return of pituitary and ovarian function, showed increasing immunoreactive inhibin levels to a maximum on day 24 (950±180 U/L). Lactating women did not show ovarian activity despite high FSH levels, and immunoreactive inhibin stayed on a low level (230±40 U/L on day 24). There was a significant correlation between immunoreactive inhibin and E 2 . Conclusions The rapid decline of immunoreactive inhibin (elimination of placental hormone) is followed by an increase in nonlactating women (production by the maturing follicle) and by persistently low levels in lactating women. The lack of adequate levels of immunoreactive inhibin in lactating women may be an explanation for the relatively high FSH levels during lactation.

Oral combination contraceptives (OCs) can exert a beneficial effect on the hypo-estrogenic condition of the lactating mother postpartum as well as on flushes and dyspareunia resulting from genital atrophy. During the 1st week after delivery there is an increased risk of thromboembolic episodes, especially for women who breast-feed. A 1989 meta analysis indicated that OC use considerably increases the risk of suspension of breast-feeding within 3 months postpartum (odds ratio 7.3). Although hormones reach the child via the mother's milk, negative consequences have not been reported. The minipills contain progestins alone, but they have been hardly used in the Netherlands because of irregular bleeding. The IUD is reliable and does not adversely affect breast-feeding, but after delivery there is an increased chance of perforation, expulsion, and infection associated with its use, especially when it is inserted in the weeks after delivery. Insertion 4-6 weeks postpartum reduces this risk. Echoscopic controls are necessary to preclude expulsion. Condoms are suitable when short-term contraception is desired before another pregnancy. They can also protect against ascending infections, but they are less reliable than OCs or the IUD. The diaphragm cannot be used in the first months because of changes in the genital tract that can occur until 3-6 months postpartum. During this time an alternative is needed, possibly the female condom. Sterilization in general should be avoided after childbirth because of the emotionally unstable period, and subsequent regret. Also postpartum sterilization is more difficult because of thickened tubes. The Bellagio consensus in 1988 recommended exclusive breast-feeding also for contraception because during the first 6 months postpartum the risk of getting pregnant is less than 2%. In the Netherlands in 1991, only 26% of women were still fully breast-feeding after 3 months. Contraceptive counseling should consider individual factors such as contraceptive experience, breast-feeding or bottle feeding, and whether the risk of pregnancy is acceptable.

SUMMARY Three patients with galactorrhoea and menstrual disturbances, due to hyperprolactinaemia and of more than 2 years duration, are described. Administration of 2-Brom-α-ergocryptine effectively lowered the plasma prolactin concentrations in all three patients and restored the normal cyclic ovarian activity. One pregnancy was noticed during therapy. The role of prolactin on ovarian function is discussed. 2-Brom-α-ergocryptine seems to be an effective drug in the long-term treatment of galactorrhoea associated with menstrual disturbances.

Serial plasma levels of prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17beta-oestradiol (E) and progesterone (P) were determined by radioimmunoassay in ten healthy women during late pregnancy and the puerperium during inhibition of lactation by Bromergocryptine. This medication was continued until the occurrence of the first menstruation, at which point an endometrial biopsy was taken. Prolactin was very effectively suppressed by Bromergocryptine in all patients, as was lactation. FSH was nearly undetectable during late pregnancy and the first week post-partum with an increase back to normal levels between day 7 and 12. Thereafter FSH levels were within the normal cyclic range. Following clearance of human chorionic gonadotrophin (HCG) during the first 2 weeks post-partum, LH was found within the normal cyclic range in all patients. From day 7 E increased in nine of ten patients to reach levels during the fourth week which are seen normally at the moment of the pre-ovulatory E-surge in cycling women. In eight of the ten cases this was concomitant with high levels of LH. The tenth patient showed a high E level at day 36. P was fully excreted within 7 days and remained low until approximately day 20. Thereafter an increase was demonstrated with levels as found during the luteal stage of the menstrual cycle in nine patients within 33 days and within 40 days in all ten patients. The endometrial biopsies showed clear signs of secretory activity. The probable action of prolactin on ovarian function is discussed. It is suggested that during the puerperium the ovaries are the more refractory part of the hypothalamicpituitaryōvarian axis, due probably to an influence of prolactin on the ovarian steroid synthesis.

summary The haemostatic and fibrinolytic properties of peritoneal fluid aspirated during laparoscopy were studied in a group of 49 women, 12 patients during the follicular phase of the menstrual cycle, and 37 during the luteal phase. Haemoglobin concentration and platelet count were low and similar in the pre- and post-ovulatory groups. Factor VIII was present in low concentrations both in the pre- and post-ovulatory period. The fibrinolytic and antifibrinolytic activity as judged by measurements of plas-minogen, α2-antiplasmin, fibrinogen degradation products, fibrinogen and antithrombin HI, rose significantly in the postovulatory period. It is concluded that the fibrinolytic activity of the peritoneal fluid depends on the stage of the menstrual cycle and is higher during the luteal phase.

SUMMARY Serial plasma levels of prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β-oestradiol (E) and progesterone (P) were determined by radioimmunoassay in ten healthy women during late pregnancy and the puerperium during inhibition of lactation by Bromergocryptine. This medication was continued until the occurrence of the first menstruation, at which point an endometrial biopsy was taken. Prolactin was very effectively suppressed by Bromergocryptine in all patients, as was lactation. FSH was nearly undetectable during late pregnancy and the first week post-partum with an increase back to normal levels between day 7 and day 12. Thereafter FSH levels were within the normal cyclic range. Following clearance of human chorionic gonadotrophin (HCG) during the first 2 weeks post-partum, LH was found within the normal cyclic range in all patients. From day 7 E increased in nine of ten patients to reach levels during the fourth week which are seen normally at the moment of the pre-ovulatory E-surge in cycling women. In eight of the ten cases this was concomitant with high levels of LH. The tenth patient showed a high E level at day 36. P was fully excreted within 7 days and remained low until approximately day 20. Thereafter an increase was demonstrated with levels as found during the luteal stage of the menstrual cycle in nine patients within 33 days and within 40 days in all ten patients. The endometrial biopsies showed clear signs of secretory activity. The probable action of prolactin on ovarian function is discussed. It is suggested that during the puerperium the ovaries are the more refractory part of the hypothalamic-pituitary-ovarian axis, due probably to an influence of prolactin on the ovarian steroid synthesis.

We investigated a possible influence of 2-bromo-alpha-ergocryptine (bromocriptine, CB 154) on the human foetus. The chromosome patterns of the children born to mothers treated with bromocriptine before conception and in early pregnancy were examined. In 19 children no numerical or structural chromosomal anomalies which might be ascribed to the use of bromocriptine could be demonstrated.

Glycosylated haemoglobin (HbA1) and glycosylated serum protein concentrations (fructosamine) were monitored in 162 normal pregnancies. The response to the standard 75 g oral glucose tolerance test (OGTT) was used to exclude gestational diabetes. A significant increase in glucose intolerance, measured from the area under the OGTT-curve ( r=0.29, P

Our interest in the peritoneal fluid was raised by the work of Maathuis in Edinburgh, in the early 1970s, later followed by the group of Koninckx in Louvain.

Puerperal lactation is regulated by a complex of hormones, including in particular prolactin. In a few instances prevention of lactation is desirable on medical grounds. However, most Western-European women who do not nurse their babies choose not to do so for personal reasons. In two double-blind studies the effect of bromocriptine was compared with that of placebo and an oestrogen/androgen compound. Bromocriptine prevented both milk secretion and engorgement of the breasts very effectively. It is clearly a better and more specific inhibitor of lactation than the combined oestrogen/androgen compound. Its effect is through the blockade of pituitary prolactin release. As normoprolactinaemia is reached, normal ovarian function is restored in bromocriptine treated women. To prevent the occurrence of a rebound lactation phenomenon, the drug has to be administered continuously for at least a fortnight.

During a laparoscopy that was performed between Day -6 and Day +9 of the cycle as related to the day of the LH peak (Day 0), the peritoneal fluid of 100 healthy female volunteers of proven fertility was collected and analysed. Peritoneal fluid volume and concentrations of total protein, albumin, alpha 1-, alpha 2-, beta- and gamma-globulins, IgA, IgG, IgM, haptoglobulin, acid-alpha 1-glycoprotein, alpha 1-antitrypsin, alpha 2-macroglobulin, C3-, C4- and C-reactive protein were determined. The peritoneal fluid volume and the concentrations of most proteins analysed showed an increase during the post-ovulatory phase of the period investigated. The peritoneal fluid:serum ratio of each individual protein showed a significant inverse correlation with its molecular weight. This confirms the assumption that peritoneal fluid is mainly an exudation product, most probably of ovarian origin.

During laparoscopy peritoneal fluid samples were collected for FSH, LH, PRL, 17 beta-estradiol, progesterone, and total protein determinations in 100 women with a normal menstrual cycle. The samples were collected between cycle day -6 and cycle day +9, with the serum LH peak as a point of reference (day 0). The period investigated was divided into seven phases. FSH and LH concentrations in the peritoneal fluid varied in a cycle-dependent pattern that reflected the pattern in serum. In every phase of the cycle, however, peritoneal fluid FSH and LH concentrations were higher than or equal to the serum levels. This finding contrasts with the physiological behavior of other proteins in the peritoneal fluid. Peritoneal fluid 17 beta-estradiol and progesterone levels also varied in a cyclic pattern, with an increase in concentration immediately after ovulation and a decrease after the midluteal phase. With the exception of 17 beta-estradiol levels during the preovulatory phase of the cycle, peritoneal fluid levels of 17 beta-estradiol and progesterone were always equal to or higher than serum levels. The increase in 17 beta-estradiol concentration in the postovulatory phase was more gradual than that in the progesterone concentration. The elevated peritoneal fluid levels of gonadotropins in the preovulatory phase of the menstrual cycle were the most striking finding of the present study. This together with the finding of high peritoneal fluid to serum ratios of steroid hormones after ovulation shed new light upon the surroundings in which follicular development, ovulation, and fertilization take place.

Summary Inhibition of lactation by the new peptide ergot alkaloid 2-Br-α-ergocryptine (CB154) was studied in a double-blind trial. Forty patients divided into four groups were treated during seven consecutive days with daily doses of either 2.5 mg., 5.0 mg., 7–5 mg. of CB154 or a placebo. In terms of milk secretion, engorgement and pain the CB154 therapy was significantly better than the placebo. Tolerance of CB154 was good and no drug-related side effects were observed. In a further trial CB154 was tried in five patients with already established lactation and in 22 patients who had not responded to standard hormonal therapy. With one exception (suppression of lactation after four months of full breast-feeding) excellent results were achieved. For prevention as well as for the suppression of already established lactation, the following dosage schedule of CB154 is effective and avoids a rebound phenomenon: 2.5 mg. twice daily for two weeks, followed by 2.5 mg. once daily for one week.