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Management of the amenorrhoea-galactorrhoea syndrome due to pituitary tumour is still controversial. However, in cases of pituitary prolactinproducing adenomas, ovulation and pregnancy are readily induced medically with bromocriptine. In our series of 14 patients conception occurred in all cases within 6 months of treatment. All of the 14 women had uneventful full term pregnancies and normal infants. Neither neurological nor visual symptoms appeared in these patients during their pregnancies. Lactation had no apparent effect on the growth of the pituitary tumour since radiological and neurological evaluations were unchanged. Prolactin levels for each patient following the termination of pregnancy and breast feeding were apparently diminished or similar to the prolactin levels obtained prior to treatment. This finding could add to the evidence that probably there was no further growth of the pituitary tumour. Three of the 14 women have had a second pregnancy without any complications. It is recommended that patients with microadenomas can be allowed to become pregnant on bromocriptine alone, provided that they are carefully supervised during pregnancy.

The effect of breast feeding on serum FSH and LH concentrations was studied in 13 puerperal women. Despite the collateral increase in serum prolactin levels, nursing was not followed by significant changes in serum FSH or LH levels during a 30-min observation period. Our data indicate that nursing has no significant effect on pituitary FSH and LH release.

The follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretory response to various stimuli was studied in 4 adult siblings with the complete form of testicular feminization. Before gonadectomy, the 4 patients had elevated serum levels of both LH and FSH. Clomiphene administered for 7 days did not change the serum levels of gonadotropins. LH-releasing hormone (LH-RH) administration resulted in FSH release above the range observed in normal adult men and women; however, the maximum LH increase was not different from that of normal adults. Gonadectomy elicited a further and significant elevation of both FSH and LH levels. After castration, serum levels of LH and FSH exhibited a further increase following LH-RH administration comparable quantitatively to that before castration. The FSH secretory response to LH-RH was greater than that of LH. The administration of progesterone alone to the 4 patients already castrated did not result in any major change in the serum levels of FSH and LH. Estrogen administration decreased the high levels of gonadotropins. The relative decrease for FSH was greater than for LH, and, when progesterone was given following 4 weeks of estrogen treatment, an increase in the serum levels of LH was found; there was also a small increase in FSH concentration. It is concluded from this study that in testicular feminization: (1) There is a partial gonadal feedback control of both FSH and LH secretion; (2) hypothalamic receptors are not sensitive to the stimulatory effect of clomiphene; (3) there is an unusually large amount of FSH released by the pituitary after intravenous LH-RH; (4) FSH and LH secretion are readily suppressed by estrogen administration; (5) there is a positive feedback effect of progesterone upon serum gonadotropins in estrogen-primed castrated patients with testicular feminization.

The effect of acute L-dopa therapy on serum FSH and LH concentrations was studied in 10 patients with the amenorrhea-galactorrhea syndrome. L-dopa ingestion was not followed by a significant alteratio

Functional pituitary reserve in 18 patients with the amenorrhea-galactorrhea syndrome was evaluated using luteinizing hormone-releasing hormone (LH-RH), l-dopa, and chlorpromazine. Gonadotropin release after administration of synthetic LH-RH varied widely from that seen in normal women to that below the normal range; however, cases with pituitary tumor exhibited the lowest responses or no responses to LH-RH. Prolactin release in response to drugs which normally either stimulate (chlorpromazine) or inhibit (l-dopa) its secretion, also varied widely regardless of the presence or not of a pituitary tumor. It is concluded that LH-RH is a reliable test to determine the pituitary reserve in cases of galactorrhea associated with amenorrhea. These results suggest that high prolactin levels associated with a deficient secretion of gonadotropin in response to LH-RH may be indicative of an underlying pituitary tumor, even in the absence of sellar enlargement.

Pituitary responsiveness to the intravenous injection of synthetic luteinizing hormone-releasing hormone (LH-RH) was studied in a female patient with Prader-Willi syndrome and the response was compare

Eleven women received synthetic LRH by a single intravenous injection 48 hr postpartum. Seven of the 11 received again LRH on day 15 postpartum. Serum concentration of FSH in the immediate postpartum and FSH and LH 15 days after delivery were measured by radioimmunoassy. Serum FSH was undetectable 48 hr following delivery and LRH failed to increase FSH concentration. On day 15 postpartum baseline levels of FSH were within normal limits and LH concentration was below normal as compared with follicular phase values of the menstrual cycle. FSH release in response to LRH was greater and LH release was diminished when compared to that observed in normal menstruating women. It is concluded that recovery of pituitary function is faster for FSH than for LH following delivery, and that 15 days after delivery a reversal from menstruating women on the FSH/LH secretory responsiveness to LRH is observed.

Luteinizing hormone-releasing hormone (LH-RH), purified from porcine hypothalami, was infused iv for 24 hours into a woman with secondary amenorrhea who was pretreated with human menopausal gonadotropin (HMG—Pergonal). Supplemental LH-RH was injected iv rapidly at 8 and 24 hours during the infusion. Ovulation, indicated by the marked rise in urinary pregnanediol levels, was confirmed by pregnancy. During a control cycle in which HMG but not LH-RH was administered, no rise in urinary pregnanediol values occurred. It is suggested that LH-RH may be useful in the treatment of some cases of infertility.

Thirteen pregnant women were given synthetic luteinizing hormone-releasing hormone (LH-RH) by a single intravenous injection. Serum concentrations of follicle-stimulating hormone (FSH) were measured by radioimmunoassay. A significant rise in FSH was found after LH-RH administration in 10 of the 13 patients; however the response was very variable in each case. The maximum increase in the serum levels of FSH above the base line remained constant with the advancement of pregnancy. The present study confirms that the pituitary gland responds to LH-RH administration with the secretion of FSH despite the high levels of sex steroid and chorionic gonadotropin during pregnancy.

The antagonistic analog of luteinizing hormone-releasing hormone (LHRH) NAc-D-p-Cl-Phe D-Trp D-Phe D-Ala -LHRH was administered intramuscularly in a dose of 2 mg to 10 normally ovulating women on day 12 of the menstrual cycle. Ovulation was inhibited in 6 patients and 2 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. (authors)

Summary Pyridoxine treatment did not inhibit milk secretion in 14 puerperal women. In contrast, romocriptine was antilactogenic. Pyridoxine appeared not to suppress prolactin secretion.

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.

A group of 17 hyperprolactinemic women was given 200 mg of nomifensine orally to evaluate its diagnostic potential to discriminate between tumors and nontumorous hyperprolactinemia. The nomifensine suppressive effect on prolactin serum levels was not significantly different between patients with or without enlargement of the sella turcica. A control group of 5 women with normal prolactin levels exhibited a nomifensine suppressive effect below 65% of the baseline prolactin level, which was significantly different from that in the hyperprolactinemic group. In conclusion it is confirmed that the nomifensine test provides no value in the early diagnosis of the prolactinoma.

14 women with elevated prolactin (PRL) serum levels (greater than 25 ng/ml) were given 2.5 mg of metoclopramide, by bolus intravenous injection, to evaluate its diagnosic potential as a stimulus for PRL release. Following metoclopramide injection there was a prompt increase in serum PRL in normal subjects and in patients with moderate PRL elevations associated with galactorrhea-oligomenorrhea. The women with amenorrhea-galactorrhea regardless of the presence of absence of a pituitary tumor, showed a blunted response. Metoclopramide failed to induce TSH secretion in all cases.the use of the metoclopramide test provides no additional clinical information to that furnished by the basal serum PRL concentration for the hyperprolactinemic patient.

An attempt has been made to pharmacologically enhance PRL secretion to improve lactation. Twenty-one puerperal women with past history of defective lactation and PRL levels under the normal range were studied for 4 weeks postpartum. Eleven patients who received orally 20 mg a day of metoclopramide showed persistently elevated basal levels of serum PRL during the four weeks' observation period. These women also had a good milk production and their infants did not need supplements. Ten women receiving placebo, however, showed an abrupt decrease in basal PRL levels, and this decrease persisted despite the continuation. Simultaneously a decline in the milk yield was observed and by the 14th postdelivery day milk production was minimal. The administration of metoclopramide at this moment to this group of poor lactating mothers produced an increase in serum PRL levels which presisted for the rest of the study. Metoclopramide also augmented the milk production so that these women were able to continue breast feeding their infants. Our preliminary results seem to prove that defective lactation associated with low prolactin levels (prolactipenia) can be treated by the manipulation of endogenous PRL secretion through the administration of metoclopramide or drugs which enhance PRL release.

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.

Summary Increased urinary oestrogen excretion was observed in 8 out of 10 oophorectomized women who were given intravenous adrenocorticotrophic hormone for two consecutive days. The maturation index of the vaginal epithelium showed an oestrogenic response.

Six women with isolated gonadotropin deficiency were stimulated with 50 μg of synthetic luteinizing hormone-releasing hormone (LH-RH) and their response was compared with that obtained from 10 eumenorrheic women. Patients with hypogonadotropic hypogonadism had low serum LH levels and normal or near

The effect of clomiphene treatment on prolactin (PRL) secretion and lactation was studied in 22 normal puerperal women (20-39 years of age). 10 patients received 100 mg clomiphene/day for 7 days and 12 were controls. All 10 receiving clomiphene had painful breast engorgement and obvious milk secretion. PRL levels were unaffected by treatment in the 5 women studied. Patients receiving placebo had a similar pattern of response.

The effect of thyrotropin releasing hormone (TRH) on the menstrual cycle of eumenorrheic women was investigated. It was reported previously that TRH therapy in baboons blocked ovulation when administered early in the menstrual cycle and produced luteolysis when given during the luteal phase of the cycle. Whether these antifertility effects were associated with elevation in prolactin (PRL) secretion or produced by another mechanism was not apparent. It has been suggested that PRL probably decreases ovarian sensitivity to gonadotropins and thereby acts as an antifertility agent during the period of puerperal lactation. In the experiment described TRH was given to 6 women for 8 consecutive days beginning Days 8 and 9 of the menstrual cycle. Daily serum samples were obtained for radioimmunoassay for LH FSH and PRL secretory response. TRH was ineffective in interfering with ovulation and failed to show significant effects on cycle lengths. Moreover the length of the luteal phase was not affected by TRH as demonstrated by basal body temperature endometrial biopsy and pregnanediol excretion. These findings are in disagreement with the recent findings in baboons receiving TRH. The study also demosntrated that TRH administration induces a PRL secretory response which blocks neither the LH surge nor the ovarian responsiveness to endogenous gonadotropins in women who menstruate normally.

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.