Edit Zylber-Haran

THE DECREASED BASAL AND STIMULATED PROLACTIN LEVELS IN ISOLATED GONADOTROPHIN DEFICIENCY: A CONSEQUENCE OF THE LOW OESTROGEN STATE

Prolactin secretion has been evaluated in seven male and six female patients with isolated gonadotrophin deficiency (IGD). The subjects were challenged with the dopaminergic antagonist, metoclopramide (10 mg) and TRH (200 μg) before, during and after cessation of hormonal treatment. Five females received three consecutive 21‐day courses of ethinyl oestradiol (0·1 mg daily) at monthly intervals and the remaining subject conjugated oestrogens (Premarin 0·625 mg daily) according to a similar protocol. Treatment of the males with hCG (pregnyl) 5000 iu twice weekly led to a rise in oestradiol and testosterone levels. Two males were receiving pergonal (human menopausal gonadotrophin) in addition. In the untreated state in both males and females, basal oestradiol and PRL levels were decreased as were the PRL responses to metoclopramide and TRH as compared with normal controls. During treatment in both groups, there was an increase in basal PRL levels as well as PRL response to the two stimuli, which became indistinguishable from the controls. Cessation of treatment was associated with a rapid decrease in basal PRL levels and PRL elevation following metoclopramide and TRH. In contrast to the effect of hCG, the administration of two non‐aromatizable androgens (mesterolone and fluoxymesterone) had no effect on basal and TRH‐induced PRL secretion. The administration of clomiphene citrate during hCG treatment in one male IGD patient produced a decrease in the basal and stimulated PRL response.

Exaggerated Prolactin Response to Thyrotropin-Releasing Hormone and Metoclopramide in Primary Testicular Failure*

Twenty-eight severely oligospermic and azoospermic men aged 20 to 42 years were challenged with luteinizing hormone (LH)-releasing hormone (LHRH), thyrotrophin-releasing hormone (TRH), and the dopaminergic antagonist, metoclopramide, given at 30-minute intervals. According to basal gonadotropin levels, the patients were subdivided into three groups: those with severe testicular failure (basal LH > 20 mIU/ml and FSH > 14 mIU/ml); those with moderate testicular failure with predominant seminiferous tubule involvement (LH < 20 mIU/ml and FSH > 14 mIU/ml) and those with mild testicular failure (LH < 20 mIU/ml and FSH < 14 mIU/ml. With one exception, mean basal prolactin (PRL) levels were normal in all patients. In all three groups, however, there was an exaggerated PRL response to TRH, the response in severe and moderate testicular failure being greater than that in mild testicular failure. The response to metoclopramide was increased only in the first two groups, not in the group with mild testicular failure. When individual patients and control subjects were considered together, the peak PRL response to TRH correlated with both basal and peak gonadotropin responses to LHRH. However, the PRL responses did not correlate with 17 beta-estradiol, estrone, testosterone, or the estradiol-testosterone ratio. It is concluded that oligospermic and azoospermic subjects with the most severe testicular failure and the highest gonadotropin levels have the greatest PRL increases after TRH and metoclopramide, indicating that the PRL response is related to the degree of testicular failure.

Prolactin response to metoclopramide and chlorpromazine in primary testicular failure and isolated gonadotrophin deficiency.

The aim of the present study was to measure the PRL response to metoclopramide (MET) and chlorpromazine (CPZ) in seventeen patients with primary testicular failure and eight patients with isolated gonadotrophin deficiency (IGD). The responses were compared with those to TRH. Basal gonadotrophins and peak responses to LHRH were increased in testicular failure and reduced in IGD. Basal PRL levels were normal in both groups of patients. However, when compared with controls, the PRL response to both MET and CPZ as well as to TRH was exaggerated in primary testicular failure, whereas the responses were decreased in IGD. In both patient groups, as well as in the controls, the PRL response to MET exceeded that to TRH and CPZ. It is suggested that alterations in the steroid milieu are responsible for the exaggerated PRL response to MET, CPZ and TRH in primary testicular failure and the reduced response observed in IGD.

CLOMIPHENE CITRATE DOES NOT MODIFY THE EXAGGERATED THYROTROPHIN RESPONSE TO THYROTROPHIN-RELEASING HORMONE OCCURRING IN PRIMARY TESTICULAR FAILURE

Patients with primary testicular failure have increased basal TSH levels and an exaggerated TSH response to TRH in the presence of normal circulating levels of thyroid hormones. In order to evaluate if this TSH profile is an oestrogenrelated phenomenon, sixteen patients with primary testicular failure were challenged with 200 μg TRH prior to and after the administration of clomiphene citrate. The latter was given in a dose of 100 mg/day for 4 weeks to ten patients; 200 mg/day for 4 weeks to three patients and 100 mg/day for 2 months to the final three patients.

Dopaminergic regulation of prolactin secretion in the hyperprolactinemic syndrome.

The prolactin responses to an oral challenge of L-dopa (0.5 g) and bromocriptine (2.5 mg) were studied in 31 hyperprolactinemic females without radiological abnormalities of pituitary fossa, in 12 hyperprolactinemic patients with minor radiological evidence suggesting the presence of a pituitary adenoma and in 16 normal volunteers in the early puerperium with physiological hyperprolactinemia. Administration of bromocriptine was followed by a similar suppression of prolactin secretion in the functional as well as the adenomatous hyperprolactinemic patients. By contrast, a significantly blunted response to L-dopa was noted in the patients with pathological hyperprolactinemia (with and without radiological abnormalities of the pituitary fossa). These results suggest that the L-dopa suppression test might serve as a reliable indicator to detect prolactin-secreting microadenomas in patients with persistent hyperprolactinemia and radiologically normal pituitary fossae.

The interrelationships between prolactin and thyrotrophin secretion following dopaminergic blockage in patients with mild hyperprolactinaemia without any demonstrable pituitary tumour.

PRL, TSH and gonadotrophin responses to the dopaminergic antagonist, metoclopramide, were studied in mildly hyperprolactinaemic patients with normal sella radiology and CT scan. Eleven female patients with basal PRL levels ranging from 23 to 124 ng/ml were challenged with intravenous metoclopramide (10 mg) and on subsequent occasions with TRH (200 μg) and LHRH (100 μg). On the basis of the PRL secretory pattern following metoclopramide and TRH stimulation, the patients were divided into two groups. Group I comprised six subjects who were PRL non‐responsive to TRH and metoclopramide. Group II (five subjects) demonstrated PRL responses to TRH and metoclopramide indistinguishable from female controls. Mean±SD basal PRL levels were 68·5 ± 29·9 ng/ml in Group I and not different in Group II (40·6±12·0 ng/ml). Basal LH levels were increased in Group II, whereas FSH was increased in Group I. Basal TSH levels were lower in Group I than the controls. Following metoclopramide, Group I patients had an increase in TSH from a basal of 2·4±0·7 μU/ml to a peak of 5·9±2·7 μU/ml (P<0·005) which occurred at 30 min. TSH values were increased above basal at all time intervals following metoclopramide. In contrast, TSH levels did not change in Group II patients or the controls after metoclopramide administration. Both patient groups had TSH responses to TRH similar to the controls. Following LHRH, the LH increase was greater in Group II and the FSH in Group I. In neither group nor the controls did gonadotrophin levels change after metoclopramide.