The effect of oral administration of thyrotropin-releasing hormone on lactation.

Sixteen puerperal women between the ages of 17-30 years, were studied in a double blind trial during the four weeks postpartum. Eight women received orally 20 mg of synthetic TRH three times a day, 30 minutes before the corresponding breast feeding; the remaining group received a placebo in the same fashion. The women receiving TRH exhibited higher basal concentrations of serum PRL as well as a higher increment in response to suckling; however, the PRL concentrations before and after breast feeding in this group were similar to those of the control group by the fourth week postpartum. TRH treatment showed no effect on the yield or content of milk during the four-week period. In a conjoint study, PRL concentrations did not rise after TRH administration in women with defective lactation, suggesting that some impairment of the PRL release mechanism was present. TRH caused no clinical hyperthyroidism in the mothers nor in the children. Serial determinations of serum T3 and TBG revealed values within the normal limits. It was also observed that TRH administration had no effect on FSH and LH secretion, and gonadotropin secretion was not inhibited despite of the increments on PRL concentrations. In both groups, suckling had no effect on serum levels of pituitary gonadotropins determined before and after breast feeding. We have concluded that in full lactating mothers: a) the oral administration of TRH produced a marked increment in PRL concentration but no significant augmentation of milk production was observed; b) in some cases of hypogalactia, TRH did not improve the milk production; and c) the PRL-enhanced secretion showed no effect on gonadotropin secretion.

Pituitary hormonal reserve in patients presenting hyperprolactinemia, intrasellar masses, and amenorrhea without galactorrhea.

The pituitary release of gonadotropins, prolactin, and TSH after the simultaneous intravenous administration of 50 mug LH-RH was 400 mug TRH was evaluated in 7 amenorrheic women with sellar enlargement and hyperprolactinemia. It was found that only minimal amounts of LH and FSH were released by LH-RH. All patients had elevated serum prolactin levels but TRH administration elicited negligible release of prolactin. This was in contrast to the normal TSH response to TRH in most of these women. It is concluded that intrasellar masses may be associated with hyperprolactinemia which does not necessarily cause galactorrhea and that impaired gonadotropin reserve correlates with the presence of amenorrhea.

Bromocriptine. Clinical experience in the induction of pregnancy in amenorrhea-galactorrhea syndrome.

This study included a group of 50 women with amenorrhea-galactorrhea who were treated with bromocriptine (2-bromo-alpha-ergocryptine). Forty-two of these patients ovulated, and 36 conceived within 8 months of treatment. The pregnancies of 30 women reached a duration of 20 weeks or longer following ovulation induced by bromocriptine. Except in 1 case which ended in 10-week spontaneous abortion, the pregnancies of 26 patients terminated in 24 single, one twin, and one triplet births. All of the 29 newborns were healthy, and no congenital malformations were detected. The main side effects during treatment were transient constipation and nausea. Following delivery, return to pretreatment status was noted in all patients, which supports the fact that bromocriptine is not a curative agent.

Premature ovarian failure and hypothyroidism associated with sicca syndrome.

Two cases of premature ovarian failure, hypothyroidism, and sicca syndrome are described. To our knowledge, this association of sicca syndrome and multiglandular deficiency has not been previously reported. The finding of specific organ antibodies, as well as antibodies to nonorgan antigens in the 2 cases studied, supports the hypothesis that these rare clinical conditions may share a common autoimmune pathogenesis.

Effect of ergonovine on prolactin secretion and milk let-down.

The effect of ergonovine maleate on prolactin secretion and lactation was determined in 10 puerperal women. Serum prolactin concentration measured by radioimmunoassay resulted in 537.2 +/- 45.9 ng/ml (M +/- SE) before the oral administration of 0.6 mg ergonovine maleate, and 89.7 +/- 25.6 ng/ml after 7 days of therapy. The serum prolactin concentration seen in the control group of nonlactating women (562.0 +/- 36.1 and 218.0 +/- 27.3 ng/ml) was significantly greater than (P less than 0.01) that seen in the treated group. In 2 additional patients it was also demonstrated that the simultaneous administration of ergonovine by oral and intravenous routes potentiates the suppressive effect on prolactin secretion. Three of the 10 treated women showed progressive inhibition of lactation. This study shows that ergonovine maleate interferes with prolactin secretion, and may decrease milk production.

Serum FSH and synthetic LHRG response in pregnant women at term and in the newborn.

Serum immunoreactive FSH was undetectable in a) pregnant women past 38 weeks of gestation, b) newborn infants, and c) anencephalic infants. The intravenous administration of 100 mug of synthetic LHRH elicited no FSH release in each instance. These results seem to indicate that the absence of FSH in serum in pregnant women in the last trimester, as well as in the newborn, is due to the suppressive effect on the anterior pituitary of the increased amount of circulating sex steroids.

Gonadotropic responsiveness to clomiphene, LRH, estradiol, and bromocriptine in galactorrheic women.

Twenty hyperprolactinemic patients with galactorrhea were studied to determine their gonadotropic responses to various stimuli. Five women lacked response to gonadotropin following the administration of clomiphene citrate. Ten patients who had luteinizing hormone releasing hormone (LRH) tests before and during bromocriptine administration exhibited varied FSH and LH responses that apparently were unaffected by bromocriptine therapy. A loss of the normal positive feedback of estrogens at the level of the hypothalamus was demonstrated in most patients before and during bromocriptine therapy. Long-term treatment with bromocriptine in 11 women resulted in a decrease of serum prolactin, cessation of lactation in all, and pregnancy in 8. These results suggest that the failure of normal secretion of gonadotropins in hyperprolactinemic women may result from 1) inadequate release of endogenous LRH, and 2) loss of the positive feedback of estrogens, as a result of the same hypothalamic disturbance that provokes the hyperprolactinemia. In turn, the elevated prolactin levels may exert a short-loop negative feedback at the hypothalamic level, inhibiting cyclic gonadotropin release.

Long-term administration of thyrotropin-releasing hormone and its effect on gonadotropin secretion in eumenorrheic women.

Thyrotropin-releasing hormone (TRH) was administered orally in doses of 60 mg/day to six women for two consecutive menstrual cycles. Daily serum samples were obtained for radioimmunoassay of luteinizing hormone, follicle-stimulating hormone, prolactin (PRL), and 17beta-estradiol secretory response. TRH was ineffective in interfering with normal gonadotropin and estradiol secretion, and failed to inhibit ovulation. The length of the luteal phase was not affected by TRH in the two cycles of treatment as demonstrated by basal body temperature, pregnanediol excretion, and endometrial biopsy. Long-term TRH administration induced an elevation of PRL serum levels that were not persistent and showed wide spikes. From these studies it is concluded that oral TRH at a dosage of 60 mg/day is unable to modify gonadotropin secretion and ovarian responsiveness in normally menstruating women.

Induction of ovulation with clomiphene and estradiol benzoate in anovulatory women refractory to clomiphene alone.

Twenty-two infertile and clomiphene-nonresponding patients received a course of clomiphene, 100 mg/day for 5 days, followed 7 days later by an intramuscular injection of 1 mg of estradiol benzoate. The diagnosis of idiopathic chronic anovulation had been established. None of these patients had galactorrhea, hirsutism, or ovarian enlargement. Thirteen of the twenty-two women had surges of both luteinizing hormone and follicle-stimulating hormone after the estradiol injection; the peak gonadotropin levels occurred within 72 hours of the injection. These 13 patients ovulated and pregnancy ensued in 10 of them. The estradiol benzoate injection also elicited a significant increase in serum prolactin levels- This enhanced prolactin release had no apparent effect on the gonadotropin surge. These results suggest that the association of clomiphene and estradiol benzoate potentiates the action of clomiphene and may prove useful in clomiphene nonresponders.

Therapeutic use of gonadoliberin (follicle-stimulating hormone/luteinizing hormone-releasing hormone) in women.

Certain conclusions may be drawn from the present review: 1. Synthetic FSH/LH-RH may induce ovulation; therefore, a therapeutic effect has been established in some cases of anovulatory infertility, but it is still difficult to assess the correct dose of FSH/LH-RH because of individual variations in response. 2. Gonadoliberin may also be used to induce ovulation after follicular maturation has been evoked by other agents. FSH/LH-RH can be utilized for supplementing the LH surge after clomiphene therapy in cases of clomiphene failure. When associated with HMG, the synthetic decapeptide may be helpful in avoiding the ovarian hyperstimulation syndrome. 3. The "triggering" of ovulation by a continuous infusion of FSH/LH-RH might be a convenient means of controlling the timing of ovulation. 4. It is expected that FSH/LH-RH blocking analogs may be used to inhibit both LH and FSH release induced by endogenous gonadoliberin in women seeking contraception.

Successful induction of ovulation with synthetic luteinizing hormone-releasing hormone in anovulatoy infertility.

PIP: 13 women with suspected hypothalamic anovulation were treated with l uteinizing hormone-releasing hormone (LH-RH) by a variety of regimens. 3 women received LH-RH by continuous intravenous infusion equal to 100 mcg LH-RH for 8 hours, followed by an acute injection of LH-RH 100 mcg. 10 days later the infusion was repeated without the supplemental injecti on and coitus advised immediately after the end of the 2nd infusion. 10 patients were given LH-RH by injection of 50 mch/day for 10 days. Coitus was indicated every other day from Day 8 of therapy. Presumptive ovulation was determined on each mode of therapy. 2 of the 3 intravenous patients had presumptive ovulation responses wihtout conception. 4 of the 10 injection patients had presumptive ovulation signs and 2 conceived. The 6 remaining injection patients responded with increased estrogens and estrogenic effect on cervical mucus. The results confirm the therapeutic role of LH-RH in certain cases of sterility.^ieng

Anovulatory effect of a LHRH antagonist in women.

The antagonistic analog of LHRH, NAc-D-p-Cl-Phe(1),(2), D-Trp(3),D-Phe(6), D-Ala(10)-LHRH was administered intramuscularly in a dose of 2 mg to ten normally ovulating women on day 12 of the menstrual cycle. Ovulation was inhibited in six patients, and two more presented an insufficient corpus luteum. No pregnancies were recorded in this series. In those patients who did not ovulate, it was demonstrated that the LHRH analog abolished the midcycle surge of both LH and FSH. Luteolysis evidenced by the rapid decline in progesterone levels was present in 2 cases. Bleeding pattern showed a tendency to delayed menses. The morphological findings in endometrial biopsies of 6 women exhibited mild proliferation. Further research along these lines is necessary for appraisal of this approach to birth control.

Correlation of optical density, lecithin and lecithin/sphingomyelin ratio in amniotic fluid.

The correlation between optical density at 650 nm, lecithin and lecithin/sphingomyelin ration was investigated in 94 amniotic fluid samples obtained from 90 patients between 28 and 40 weeks of pregnancy. All samples were processed immediately and those contaminated with blood or meconium were discarded. The correlation coefficient between lecithin and absorbance was high (0.926). The lecithin/sphingomyelin ratio also had a good correlation coefficient with the optical density (0.768). We conclude that absorbance at 650 nm is a reliable test for assessing fetal lung maturation.

Feedback effect of estradiol on follicle-stimulating hormone and prolactin secretion during the puerperium.

Injections of 3 mg of estradiol benzoate were given to seven lactating women during the second and third weeks postpartum to study its effects on secretion of follicle-stimulating hormone (FSH) and prolactin during the subsequent 4 days. Administration of estradiol during te second week postpartum had no effect on serum levels of FSH and prolactin, however, 1 week later estradiol injection elicited a double effect: FSH levels decreased and prolactin concentrations increased. Early lactation seems to abolish the estrogen induced positive feedback effect on pituitary gonadotropin secretion. The negative effect of estrogen on FSH secretion and the positive effect on prolactin release became evident by the third week postpartum.

Relationship of maternal, fetal, and amniotic fluid prolactin levels.

Serum prolactin (PRL) was measured by radioimmunoassay in 80 women in serum and amniotic fluid during various stages of normal pregnancy and at delivery. In addition, prolactin levels were measured in cord sera at 60 newborns. PRL levels in maternal serum progressively increased during pregnancy, and they were lower than the corresponding levels in amniotic fluid. A relative decline in the amniotic fluid prolactin between the 39th and the 40th week of gestation was observed. The mean concentration of PRL in umbilical blood was significant lower than that in maternal blood at delivery. The lack of correlation between the PRL in amniotic fluid and the levels found in maternal and newborns serum suggests an independient source of PRL in each of the three compartments.

[Effect of ultrafiltered peritoneal fluid from patients with pelvic endometriosis on the in vitro motility of their spouse's sperm]. / Efecto del líquido peritoneal nativo y ultrafiltrado de pacientes con endometriosis pélvica sobre la motilidad espermática in vitro de sus cónyuges.

Recently, there has been information about the ultrafiltrated peritoneal fluid in patients with endometriosis, containing macromollecules that diminish tubal fimbria action, and the in vitro ovular captation in experimental animals. In order to investigate the presence of these substances in the peritoneal fluid, and to know the possible effect that could have on spermatic motivility in vitro, of their mates; 11 sterile women with diagnosis of pelvic endometriosis, and 11 normal fertile women, were studied. On the other side, the same day of study, the mate of each of these women, produced semen obtained by masturbation, where amount and motility of sperm, in basal conditions, and after, it was capacitated with Ham-F10, were determined. The final results was evaluated as to percentage of spermatozoon with excellent and progressive motility, and percentage of motionless spermatozoo as well as based on average values (mean +/- EE), of each one of them. The statistic analysis of differences was done by t Student that in coupled samples. The results confirm that peritoneal fluid of patient with endometriosis contains macromollecules, and it shows that these substances affect the motility in vitro of mate's spermatozoon, which could explain, partially at least, the origin of sterility in this disease.