Plasma homocysteine and menopausal status.

The aim of the study was to measure the concentrations of plasma homocysteine in premenopausal and postmenopausal women, and to examine a possible relationship between plasma homocysteine and oestrogen status. Homocysteine metabolism was studied by a standardized oral methionine loading test, and oestrogen status was assessed by the measurement of serum 17 beta-oestradiol. Forty-six premenopausal and 26 postmenopausal healthy women without a history of vascular disease or adverse pregnancy outcome were recruited by public advertisement. The main outcome measures were the concentrations of fasting and postmethionine plasma homocysteine, and serum 17 beta-oestradiol. Fasting plasma homocysteine concentrations (mean +/- SD) were significantly higher in postmenopausal women as compared to premenopausal women (12 +/- 4 mumol L-1 and 10 +/- 3 mumol L-1, respectively) as well as postmethionine plasma homocysteine concentrations (46 +/- 16 mumol L-1 and 32 +/- 9 mumol L-1, respectively). In premenopausal women, postmethionine plasma homocysteine was negatively and significantly correlated to serum 17 beta-oestradiol (r = -0.34). It is concluded that plasma homocysteine concentrations, both fasting and after methionine loading, are significantly higher in postmenopausal women than in premenopausal women. In premenopausal women, the higher concentrations of serum 17 beta-oestradiol may account in part for the lower concentrations of postmethionine plasma homocysteine.

Circulating inhibin levels in lactating and nonlactating women.

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, E2, 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 E2. 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 of the relatively high FSH levels during lactation.

Hormone replacement therapy may reduce high serum homocysteine in postmenopausal women.

In a prospective study we investigated the possible changes in fasting serum total homocysteine concentrations during continuous micronized 17 beta-oestradiol, 2 mg daily, in combination with cyclic dydrogesterone, 10 mg daily during the first 14 days of each 28 day cycle, in 21 healthy non-hysterectomized postmenopausal women. During the first six cycles mean serum homocysteine decreased by 10.9% (P = 0.013), after which no further significant changes were found during the 2 years of treatment. A 16.9% decrease (P = 0.017; n = 8) was found in women with high homocysteine concentrations, while in women with low homocysteine concentrations (n = 13) no significant changes were observed. The observed decrease in high homocysteine concentrations in postmenopausal women may in part contribute to the decreased risk of developing cardiovascular disease during hormone replacement therapy.

[Contraception following pregnancy]. / Anticonceptie na een bevalling.

PIP: 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.^ieng

Antisperm antibodies and in vitro fertilization.

The purpose of this study was to investigate the influence of antisperm antibodies in the male, the female, or both partners on the outcome of in vitro fertilization treatment. The results in terms of ongoing pregnancies in the male and female antibody-positive group were the same as in the antibody-negative group. In the double antibody-positive group two of the three patients became pregnant. When high levels of antisperm antibodies were present on the spermatozoa, the fertilization rate was significantly reduced. In the female positive group no clear relationship between the antibody titer and the fertilization percentage could be detected. Abnormal semen quality was responsible for a much lower fertilization rate than the presence of antibodies. The conclusion of this study is that in vitro fertilization provides an equal change of conception in couples with antisperm antibodies in comparison with couples with no antibodies if the other semen parameters are normal.

Pulsatile secretion of luteinizing hormone and prolactin in lactating and nonlactating women and the response to naltrexone.

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.

Lactation inhibition by a single injection of a new depot-bromocriptine.

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 depot-form in 61 postpartum women. Bromocriptine rapidly increased after injection and prolactin was effectively suppressed during the study-period 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 post-partum lactation.

Postpartum return of pituitary and ovarian activity during lactation inhibition with the new dopamine agonist CV 205-502 and during normal 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.

Effect of Bellergal Retard on climacteric complaints: a double-blind, placebo-controlled study.

The effect of Bellergal Retard (BR) on climacteric complaints was evaluated versus a placebo in an 8-wk double-blind study, followed by a 4-wk open study in which only BR was used as medication. There was a marked decrease in complaints in both the BR and the placebo groups. Statistically significant differences were observed between the groups after 2 and 4 wk of treatment, indicating superior results with BR. After 8 wk of study however, these differences were no longer apparent. It was concluded that studies on medication for climacteric complaints should not only be placebo-controlled, but also be of at least 8 to 12 wk duration for proper evaluation.

Glycosylated serum proteins and glycosylated haemoglobin in normal pregnancy.

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 less than 0.0005) and a highly significant decrease in serum albumin concentration (r = -0.79, P less than 0.0005) due to the redistribution of body water, as occurs during pregnancy, resulted in a statistically significant decrease in serum fructosamine concentration (r = -0.23, P less than 0.01) when related to gestational age in weeks.

Patterns of changes in proteins in the peritoneal fluid of women during the periovulatory phase of the menstrual cycle.

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.

Patterns of changes in glycoproteins, polypeptides, and steroids in the peritoneal fluid of women during the periovulatory phase of the menstrual cycle.

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.

Haemostatic and fibrinolytic properties of peritoneal fluid in the menstrual cycle.

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 plasminogen, alpha 2-antiplasmin, fibrinogen degradation products, fibrinogen and antithrombin III, 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.

Inhibition of puerperal lactation by bromocriptine.

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.

Chromosomal patterns of children born after induction of ovulation with bromocriptine.

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.