Gonadotropin response to luteinizing hormone releasing hormone in hyperthyroid patients with menstrual disturbances

This study was designed to investigate the gonadotropin response to luteinizing hormone releasing hormone (LHRH) in patients with hyperthyroidism, as related to the presence or absence of menstrual disorders. Forty-one Japanese women with hyperthyroidism were separated into groups on the basis of the presence of a regular menstrual cycle, hypomenorrhea, or amenorrhea and further subdivided into the phase of the menstrual cycle at the time of testing. The findings in these groups were compared with those in normal subjects with respect to thyroid function, basal serum LH and FSH levels and serum LH and FSH responses to LHRH, and basal estradiol levels. Serum LH responses to LHRH were increased over normal subjects in those with hyperthyroidism regardless of the phase of the menstrual cycle and regardless of the presence or absence of menstrual disturbances. However, these augmented LH responses to LHRH were less marked in those with menstrual disorders than in those with regular menstruation. Both basal serum FSH and peak serum FSH response to LHRH were also increased in the follicular phase but not in the luteal phase of the cycle in hyperthyroid patients, regardless of menstrual function. These results suggest that high levels of circulating thyroid hormones augment the gonadotropin response to LHRH, and that increased LH and FSH secretion probably maintains the normal cyclic pituitary gonadal axis function in patients with hyperthyroidism.     

TESTICULAR FUNCTION AFTER RENAL TRANSPLANTATION

Gonadal function was assessed in seventeen adult male renal transplant recipients, with well established good homograft function, for a mean of 4.9 years. Patients were assessed clinically and by measurement of basal concentrations of FSH, LH, prolactin, testosterone and oestradiol, FSH and LH responses to bolus injections of LHRH and semen analysis. Retrospectively all had symptoms consistent with marked hypogonadism prior to transplantation but in nine out of sixteen this was reversed with transplantation. Residual hypogonadism was evident in seven of sixteen patients and correlated with duration of haemodialysis longer than 1 year (P less than 0.01). Even among patients with clinically normal gonadal function, defects in the hypothalamic--pituitary--testicular axis remained. Elevated basal serum FSH, excessive FSH responses to LHRH and lowered basal serum testosterone were found. In the group with residual hypogonadism more marked changes, including elevated basal LH and excessive LH responses to LHRH, were also found. Fertility was recorded in two men on three occasions since transplantation. Sperm counts were normal in five and abnormal in four patients. Testicular volume and sperm density were inversely correlated with basal and stimulated FSH and LH levels.     

SUPRANORMAL FSH RESPONSE TO GONADOTROPHIN-RELEASING HORMONE IN OLIGOSPERMIC MEN WITH A NORMAL BASAL SERUM FSH CONCENTRATION

Twenty-six men with severe oligospermia (sperm density less than 10 X 10(6)/ml, but greater than O), but normal serum concentration of FSH, as well as normal serum concentrations of LH and testosterone, were given a 250 microgram i.v. bolus dose of synthetic gonadotrophin releasing hormone (LHRH). The serum FSH and LH responses were compared to those of a group of normal men and a group of men with oligospermia or azoospermia and elevated basal serum FSH concentration. The mean FSH response to LHRH of the men with oligospermia but normal basal serum FSH concentration was 911 miu min/ml, nearly three times that of the normal men, 322 miu min/ml (P less than 0.001), though not so great as that of the men with oligo/azoospermia and elevated basal FSH concentration (2890 miu min/ml). Ten of the twenty-six men with oligospermia and normal basal serum FSH had a supranormal FSH response to LHRH. The mean LH response to LHRH of the men with oligospermia and normal basal serum FSH levels was not significantly different from that of the normal men. We conclude that LHRH stimulation can often elicit a deficiency of feedback inhibition of FSH secretion not readily recognizable by measurement of the basal serum FSH concentration.     

HORMONAL CHANGES ASSOCIATED WITH TESTICULAR ATROPHY AND GYNAECOMASTIA IN PATIENTS WITH LEPROSY

Basal LH, FSH, 17 beta-oestradiol and testosterone and the gonadotrophin responses to luteinizing hormone releasing hormone (LHRH) were studied in male patients with leprosy (twenty-four with lepromatous and six with tuberculoid leprosy). The mean basal LH and FSH was significantly elevated in the lepromatous group and was associated with an excessive response of both gonadotrophins following LHRH administration. The mean basal testosterone and 17 beta-oestradiol values in the lepromatous group were significantly lower than those of the tuberculoid and control groups. The abnormal gonadotrophin and sex steroid values in the lepromatous group are in keeping with the testicular atrophy and gynaecomastia accompanying this form of leprosy. However, the lack of a significant correlation between basal FSH and testicular atrophy should be noted. In addition, no correlation between any of these hormonal values and gynaecomastia could be demonstrated. The patients with tuberculoid leprosy had essentially normal hormonal profiles (except for two who had raised 17 beta-oestradiol values). This is compatible with the lack of gonadal involvement in these patients.     

The combined pituitary function test in children: an evaluation of the clinical usefulness of TRH and LHRH stimulation tests through a retrospective analysis of one hundred and twenty six cases

OBJECTIVE: The combined pituitary function test is routinely used in the endocrine investigation of short children. The TRH and luteinising hormone-releasing hormone (LHRH) response tests have been shown to be of minimal value in adults. We have evaluated the clinical utility of these tests in the context of combined pituitary function testing in children. DESIGN: A retrospective analysis of basal hormone measurements and pituitary stimulation tests in relation to clinical assessment of pituitary function. PATIENTS: One hundred and twenty-six children, 82 boys and 44 girls, aged 2-17 years, who had undergone pituitary function testing were studied. RESULTS: The TSH response to TRH stimulation correlated directly with basal plasma TSH but not basal plasma total T4. In patients with an impaired response to stimulation, basal TSH concentrations were <2.0 mIU/l and significantly lower than in patients with a normal response (P < 0.0001). An impaired response to TRH stimulation had a positive predictive value of 0.43 and a negative predictive value of 0.90 for the diagnosis of hypopituitarism. A basal TSH concentration of <2.0 mIU/l had a positive predictive value of 0.22 and a negative predictive value of 0.92. A low basal T4 (normal range 60-140 nmol/l) in combination with an inappropriately low or normal basal TSH was always associated with a diagnosis of hypopituitarism. The responses of plasma LH and FSH to LHRH stimulation correlated directly with basal plasma LH and FSH concentrations. Basal gonadotrophin concentrations, basal sex hormone concentrations or response to LHRH stimulation could not distinguish patients with constitutional delay of growth and puberty from those with hypopituitarism. There was no apparent relationship between either basal gonadotrophin concentrations or response to LHRH stimulation and clinical assessment of pituitary function. In patients > or =13 years with constitutional delay of growth and puberty the median and interquartile ranges of basal LH and FSH were 1.4 IU/l (0.7-3.6) and 2.6 IU/l (2.2-5.2) respectively. The three hypopituitary patients in this study with chronological age > or =13 years had undetectable concentrations of both gonadotrophins. The response of LH and FSH to LHRH stimulation was significantly lower in patients > or =13 years with clinical hypopituitarism than in those with intact pituitary function (P <0.02). CONCLUSION: TRH and LHRH tests in children with short stature appear to have little value over and above the baseline hormone measurements. An abnormal response to hormone stimulation is not diagnostic of hypothalamic-pituitary disease. We have demonstrated that neither TRH nor LHRH stimulation tests should be routinely used in the investigation of children with short stature.     

GONADOTROPHIN LEVELS IN WOMEN WITH CUSHING''S SYNDROME BEFORE AND AFTER TREATMENT

Basal serum concentrations of LH and FSH and their response to LHRH were studied in twelve pre- and ten post-menopausal women with Cushing's syndrome before and after treatment. Subnormal basal concentrations of LH were found in twelve out of twenty-two, and of FSH in ten of the twenty untreated patients. There was a correlation between the urinary free cortisol (UFC) and basal LH values, r = -0.59 (P less than 0.05), and UFC and basal FSH values, r = -0.76 (P less than 0.02) in the premenopausal women. All seven patients with a UFC value greater than 1080 nmol/24 h (normal range less than 270) had both a subnormal basal gonadotrophin level and a subnormal response of at least one gonadotrophin to the releasing hormone. In those patients in whom successful remission was obtained and who did not require replacement therapy, subnormal basal gonadotrophins were usually restored towards or into the normal range. It is concluded that while gonadotrophin levels may be normal in women with Cushing's syndrome, they are subnormal in those with the highest cortisol values. This may be due to a direct suppressive effect of cortisol on the release of stored pituitary hormone, and/or on LHRH release from the hypothalamus.     

EFFECT OF INTRANASAL LHRH THERAPY ON PLASMA LH, FSH AND TESTOSTERONE, AND RELATION TO CLINICAL RESULTS IN PREPUBERTAL BOYS WITH CRYPTORCHIDISM

Synthetic LHRH (HOE 471) administered intranasally over a period of 4 weeks for treatment of uni- or bilateral cryptorchidism in nineteen otherwise healthy prepubertal boys led to increased basal and peak LH values and to markedly decreased peak FSH values in the i.v. LHRH test. Basal testosterone remained unchanged. Sixteen cryptorchid boys treated with placebo served as a control group. The reduced FSH response to i.v. LHRH could be due to induction of a gonadal feedback mechanism rather than pituitary depletion of FSH, in view of the favourable therapeutic effect and the increased LH secretion seen in some of our patients. Pretreatment LHRH tests were available in twenty successfully and in twenty-eight unsuccessfully treated boys. LH values were similar in both groups, whereas FSH peak values were significantly higher in boys who responded successfully to subsequent therapy. Testicular descent occurred most readily in boys with a large pool of easily releasable FSH and without a significant rise in testosterone (in contrast to HCG treatment). We suggest that FSH induces changes that potentiate the local action of testosterone.     

PRIMARY HYPOTHYROIDISM OF CHILDHOOD: EVALUATION OF THE HYPOTHALAMIC-PITUITARY GONADAL AXIS BEFORE AND DURING L-THYROXINE REPLACEMENT

Hypothyroidism is frequently associated with abnormal sexual development. To determine the longitudinal influence of thyroxine replacement on the hypothalamic pituitary gonadal axis, we studied five prepubertal hypothyroid girls and two boys before, and all the girls six weeks and one year after, thyroxine replacement. All girls showed significantly elevated basal gonadotrophin concentrations before treatment. Following one year of therapy, despite all girls having begun puberty, basal gonadotrophin concentrations were significantly decreased in the four euthyroid girls as compared with our normal pubertal girls. The fifth girl studied at one year was hypothyroid at the time of testing and her gonadotrophin values were increased even above previous basal values. Pretreatment serum TSH values inversely correlated with maximum pretreatment incremental LH (r = -0.54) and FSH (r = -0.52) responses to LHRH. Serum TSH values directly correlated with PRL concentrations (r = +0.82). Of the two hypothyroid boys evaluated, Patient 1 was mildly hypothyroid and showed normal prepubertal basal LH, FSH, testosterone and low normal LHRH responsiveness. Patient 2, who was more severely hypothyroid, had elevated basal gonadotrophin secretion and responsiveness to LHRH but prepubertal testosterone concentrations. These data indirectly show that thyroxine may increase the biological/immunological potency of gonadotrophins. The elevated gonadotrophin values in the hypothyroid state suggest that the metabolic clearance rate of gonadotrophins is prolonged. The more severe the elevation in TSH secretion, the more marked was the alteration in the hypothalamic pituitary axis in respect to PRL secretion and delta max LH and FSH response to LHRH. Replacement with thyroxine was followed by normal pubertal development, and normal pubertal oestradiol and PRL concentrations, despite low immunoreactive gonadotrophin secretion.     

Pituitary and gonadal function in prepubertal and pubertal cryptorchidism

LRH and hCG tests were performed in 35 prepubertal and 35 pubertal boys with unilateral or bilateral cryptorchidism to examine the pituitary and gonadal function. Twenty-one normal boys were also examined as controls. In the prepubertal group, distinct increases in serum LH, FSH and testosterone levels by LRH and hCG tests were found in all of the normal and unilateral cryptorchid boys. However, no or very little response was observed in 4 out of 17 boys with bilateral cryptorchidism. In the pubertal group, serum levels of LH, FSH and testosterone in normal boys, in unilateral and in bilateral cryptorchid boys were evidently higher than those in the prepubertal group, and distinct or moderate responses by the LRH and hCG tests were found in all boys examined. Although serum testosterone levels were similar in all groups, serum basal and peak gonadotrophin levels by the LRH test were significantly higher in bilateral cryptorchid boys than in normal and unilateral cryptorchid boys. The difference was more marked in FSH than in LH level. An elevated level of serum LH is suggestive of the hypofunction of not only the seminiferous tubules but also of the Leydig cells in cryptorchid testes.     

OESTROGEN MODULATION OF GONADOTROPHIN AND PROLACTIN RELEASE IN WOMEN WITH ANOVULATION AND THEIR RESPONSES TO CLOMIPHENE

An LHRH test was performed before and at both 44 and 92 h after the administration of 2.5 mg oestradiol benzoate in eleven patients with hyperprolactinaemia, eight with idiopathic secondary amenorrhoea and seven with oligomenorrhoea. The basal serum hormone concentrations and the responses to LHRH were compared with the same tests performed on ten normal subjects during the early follicular phase of their menstrual cycles (days 4--6). Mean basal concentrations of oestradiol in each group of patients and oestrone in those with hyperprolactinaemia were significantly lower than in the normal subjects. The mean concentration of prolactin in women with secondary amenorrhoea remained lower than in the normal women throught the tests (P less than 0.05). The LH and FSH responses to LHRH before oestrogen in patients with hyperprolactinaemia and of FSH in those with secondary amenorrhoea, were greater than in the normal subjects (P less than 0.001). After oestrogen treatment the responses were similar in all groups except in those with oligomenorrhoea where LH and FSH responses at 44 h (P less than 0.05 and P less than 0.01 respectively) and LH responses at 92 h (P less than 0.01) were lower than in normal controls. The responses at 92 h in all groups were greater than at 44 h (amplification) but the amplification at 92 h and at 44 h compared to the pre-treatment responses, tended to be lower in each group of patients compared to the normal controls. In the hyperprolactinaemic group of patients there was a negative correlation between the basal prolactin concentration and the gonadotrophin amplifications at 92 h (P less than 0.01), and a positive correlation between the basal oestrone levels and the amplifications at 92 h (P less than 0.01). The results of the oestrogen amplification test in eleven of the non-hyperprolactinaemic anovular patients were compared with the ovulatory response to 100 mg clomiphene given for 5 days. Six showed a normal oestrogen amplification and they all ovulated. Two patients failed to show greater amplification at 92 than at 44 h and required human chorionic gonadotrophin (HCG) as well as clomiphene to ovulate. The other three showed a diminished LH amplification at 92 h; they required 200 mg clomiphene and showed a prolonged follicular phase. The responses of the hyperprolactinaemic patients to clomiphene were poor and there was a negative correlation between prolactin concentration and oestrogen production (P less than 0.01). All ten hyperprolactinaemic patients treated with bromocriptine ovulated and eight conceived. The oestrogen amplification test appears to have some value in predicting the subsequent response to clomiphene in non-hyperprolactinaemic anovular women.     

MEASUREMENT OF GONADOTROPHINS, TESTOSTERONE, Δ4 ANDROSTENEDIONE AND DIHYDROTESTERONE IN IDIOPATHIC OLIGOSPERMIA

Basal concentrations of FSH, LH, testosterone, delta4 androstenedione and dihydrotestosterone, together with FSH and LH responses to single injections of LHRH were determined in eighty-four patients with oligospermia and in twenty-seven normal men. LHRH responses were heterogeneous and indicate that various disorders might cause this syndrome. In six cases there appeared to be an isolated deficiency in spermatogenesis, as indicated by an increased FSH response, whilst the LH response was normal as were the concentrations of the testicular hormones. In twenty cases a concomitant disorder of Leydig cell function and spermatogenesis is suggested as indicated by increased FSH and LH responses and decreased concentrations of testosterone and delta4 androstenedione (six) or concentrations at the lower limit of normal (fourteen). Furthermore, in five cases a hypothalamic and/or pituitary disturbance may be accepted on the basis of normal or decreased basal concentrations decreased and responses to LHRH with decreased concentrations of testosterone and delta4 androstenedione. Finally, in thirty-seven cases, oligospermia was not associated with any modification basal gonadotrophin concentrations or response to LHRH when compared with normal subjects.     

alpha-Subunit and gonadotropin responses to luteinizing hormone-releasing hormone in hyperprolactinemic women before and after bromocriptine

alpha-Subunit and gonadotropin responses to a LHRH infusion (0.2 micrograms/min) for 4 h were studied in eight hyperprolactinemic amenorrheic women, ages 23-40, and in five normal women in the early follicular phase of the menstrual cycle. Basal alpha-subunit and LH concentrations were comparable to normal women; however, basal FSH concentrations were significantly (P less than 0.05) lower. Peak serum alpha, LH, and FSH concentrations during the LHRH infusion were significantly higher than controls (P less than 0.01, P less than 0.05, and P less than 0.01, respectively). Gel chromatography of serum confirmed the presence of both free alpha-subunit and intact LH which had normal biological activity. Six of the women were restudied in the early follicular phase of the cycle after return of normal ovulatory function and normalization of serum PRL concentrations. During bromocriptine therapy, peak serum alpha, LH, and FSH concentrations decreased significantly (P less than 0.02, P less than 0.05, and P less than 0.001, respectively) and were comparable to control subjects. The changes in serum alpha and gonadotropin responses to the LHRH infusion during bromocriptine therapy occurred independently of the serum estradiol concentrations. Abnormalities in the regulation of alpha-subunit and gonadotropin secretion are present in hyperprolactinemia. These abnormalities reverse with bromocriptine therapy and may occur independently of changes in gonadal steroids.     

藏族男性肝病患者下丘脑-垂体-性腺轴功能的变化及其临床意义

目的　探讨藏族男性肝病患者下丘脑 垂体 性腺轴的变化 ,了解不同类型肝病患者性腺激素水平的变化 ,协助临床对病情和预后的判断。方法　于 1999- 12～ 2 0 0 4 - 0 4在西藏自治区第二人民医院随机选择西藏地区藏族男性肝病患者 93例 ,包括甲型肝炎、乙型肝炎、酒精性肝病、肝硬化及重症肝炎。同时选取西藏地区 19名健康藏族男性作为对照。测定入选者睾酮 (T)、雌二醇 (E2 )、卵泡刺激素 (FSH)、黄体生成素 (LH )、泌乳素(PRL)及促性腺激素释放激素 (LHRH)的水平。资料统计采用双侧 t检测。结果　肝病患者E2 、PRL和LHRH水平与对照组比较均有显著性差异 (P <0 0 1、P <0 0 1、P <0 0 5 )。急性肝炎T、E2 、PRL升高 ,E2 升高 (P <0 0 1、P <0 0 5、P <0 0 1)。出现高雌激素血症和低睾酮血症 :重症肝炎T、FSH、LH、LHRH降低 (P <0 0 1、P<0 0 5、P <0 0 5、P <0 0 1) ,E2 、PRL升高 ,均为P <0 0 1。结论　性激素水平的变化与肝功能受损程度相一致 ,因此临床上测定性激素水平对了解病情、判断预后有着一定的作用。     

GONADOTROPHIN AND ALPHA SUBUNIT SECRETION BY HUMAN ''FUNCTIONLESS'' PITUITARY ADENOMAS IN CELL CULTURE: LONG TERM EFFECTS OF LUTEINIZING HORMONE RELEASING HORMONE AND THYROTROPHIN RELEASING HORMONE

The long-term effects of LHRH and TRH on gonadotrophin alpha subunit, FSH and LH secretion by cell cultures of four human chromophobic pituitary tumours have been examined. The tumours derived from one male and three female patients who presented because of visual disturbance but had no evident endocrine symptoms. Subsequent serum hormone analysis showed the FSH to be high in the male but low or normal in the post-menopausal females whereas LH levels were low in all patients. In culture, basal hormone secretion could be maintained for periods up to 63 d. All tumours secreted alpha subunit and FSH, but much lower amounts of LH. Addition of LHRH or TRH for a period of 12 to 41 d showed that alpha subunit, FSH and LH secretion were stimulated by LHRH from one tumour, by LHRH and TRH from two tumours. There was always a rapid decline in the LH secretion. The tumour which secreted FSH predominantly was stimulated by TRH. We conclude that human pituitary 'functionless' adenomas can secrete gonadotrophin alpha subunit and FSH in vitro and that secretion can be stimulated during long term releasing hormone experiments. LH secretion, however, cannot be maintained.     

ENDOCRINE FUNCTION IN THE PRADER-WILLI SYNDROME

Hypothalamic, pituitary and gonadal function was studied in five male and three female patients with the Prader-Willi syndrome. All were clinically hypogonadal: all males had low circulating testosterone levels, although in two females basal plasma oestradiol was within the normal range for the early follicular phase of the menstrual cycle. Basal gonadotrophin levels were low and the response to the intravenous administration of LHRH was subnormal in seven. Repeat administration of LHRH after 10 days and 6 weeks treatment with oral clomiphene (200 mg daily) was followed by a normal rise in luteinizing hormone (LH) and follicle stimulating hormone (FSH) in four out of five patients tested. All five males were tested with human chorionic gonadotrophin (hCG) and the rise in plasma testosterone was subnormal in four. Treatment with hCG was continued for 6 weeks in these four patients, but in only one did testosterone levels rise (transiently) to the normal adult male range. In one female patient studied no rise in plasma oestradiol was detected in response to human menopausal gonadotrophin (hMG). These results suggest that the hypogonadism in the Prader-Willi syndrome is due to combined hypothalamic and primary gonadal abnormalities.     

Modulation of rat pituitary gonadotrophin secretion by porcine granulosa cell 'inhibin', LH releasing hormone and sex steroids in rat anterior pituitary cells in culture

The incubation of female rat adenohypophysial cells in primary culture with porcine granulosa cell culture medium (GCM) led to the complete inhibition of responses of LH and FSH to LH releasing hormone (LHRH) as well as to the inhibition of spontaneous release of FSH. These effects of GCM suggest the specificity of the 'inhibin'-like activity of this material. Granulosa cell culture medium completely reversed the stimulatory effect of oestradiol-17 beta on the responses of LH and FSH to LHRH, as well as reversing the stimulatory effect of progesterone, oestradiol or a combination of both steroids on the spontaneous release of FSH, while not affecting the spontaneous release of LH. The antioestrogenic effects of progesterone observed on the response of LH to 0.3 nM-LHRH were amplified in the presence of GCM while the stimulatory effects of progesterone, oestradiol or both on the response of FSH to 0.3 nM-LHRH were completely reversed by the medium. Moreover, the presence of GCM led to an additive inhibitory effect with dihydrotestosterone on the response of LH to LHRH while it completely reversed the stimulatory effect of the androgen on spontaneous and LHRH-induced FSH release. The present data show that the presence of porcine granulosa cell 'inhibin' activity can exert marked interactions with sex steroids in the control of gonadotrophin secretion. This 'inhibin' activity reversed all the stimulatory effects and potentiated all the inhibitory effects of sex steroids on gonadotrophin secretion. Although the physiological role of 'inhibin' remains to be defined well, the importance of this activity is clearly demonstrated in anterior pituitary cells in culture.     

CLINICAL AND ENDOCRINE FEATURES OF HYPERPROLACTINAEMIC AMENORRHOEA

The clinical, radiological and endocrine findings in thirty-five women with hyperprolactinaemia and amenorrhoea are described. Twelve patients had radiological evidence of a pituitary tumour and six were tested after pituitary ablation. Seventeen patients with hyperprolactinaemia and normal pituitary X-rays were also studied. None was on any drug known to increase prolactin secretion and all patients were euthyroid when tested. Basal serum prolactin concentrations were high in the group with untreated pituitary tumours and in those with normal X-rays. The levels were variable in the post-ablation cases. The increase of prolactin after TRH was subnormal in all of the groups. Serum oestradiol concentrations were low in most patients and nineteen of twenty-one patients tested had no withdrawal bleeding after treatment with a progestogen. Mean serum gonadotrophin concentrations (basal and after LHRH) were normal in twenty-nine patients but subnormal in four post-ablative cases. Anovulatory responses to clomiphene were obtained in nineteen of twenty patients tested. Fifteen patients were treated with bromocriptine; twelve ovulated and eight became pregnant; two not responding had impaired LH and FSH production. Hyperprolactinaemic amenorrhoea is a common disorder with characteristic endocrine features. Galactorrhoea is unusual (30%). Treatment with bromocriptine lowers prolactin concentrations and rapidly repairs the reproductive defect.     

HYPERPROLACTINAEMIA AND IMPOTENCE

Clinical, laboratory and radiological findings were evaluated in twenty-nine men who had raised serum prolactin concentrations and pituitary tumours. Twenty-one had functionless pituitary tumours ('prolactinomas') and eight had acromegaly. Suprasellar extension was detected in twenty of the twenty-six men who had lumbar airencephalography. Three patients were studied before, sixteen before and after and ten only after pituitary ablative therapy.
Seventeen of these men complained of complete lack of libido and impotence and six had impaired libido and sexual potency; only six patients in this series denied reproductive symptoms. Thirteen of the impotent subjects had small soft testes, ten reduced facial and body hair and three had marked gynaecomastia. No features of hypogonadism were noted in the six patients without reproductive symptoms and none of the patients had galactorrhoea.
Serum prolactin concentrations were higher and serum testosterone concentrations lower in the impotent men compared with those with normal sexual potency. Serum LH and FSH (both basal and in response to LHRH), oestradiol and oestrone concentrations were not different between the two groups and, except in those with post-operative hypopituitarism, were within the normal range. Following successful lowering of prolactin concentrations by surgery or bromocriptine or both, serum testosterone rose and potency returned; by contrast failure to lower prolactin concentrations was associated with persistent impotence and hypogonadism.
The endocrine profile of low serum testosterone concentrations with gonado- trophins which had not risen into the range usually seen in primary hypogonadism (together with the parallel increase of LH and testosterone in one patient studied sequentially during treatment which suppressed prolactin levels to normal), suggested that the impaired gonadal function was caused by a prolactin-mediated disturbance of hypothalamic-pituitary function.     

OESTROGEN-GONADOTROPHIN FEEDBACK MECHANISMS IN THE PUERPERIUM

The effect of oestradiol benzoate on serum gonadotrophin concentrations before and after LHRH administration was studied in lactating and non-lactating women at 3 and 6 weeks post-partum. Except in the non-lactating women at 6 weeks, basal serum FSH concentrations were suppressed by oestrogen. There were no significant changes in basal concentrations of LH after oestrogen in the lactating women in either the 3- or 6-week studies. Individual increases in the basal LH concentrations in two out of six non-lactating subjects in the 6-week study occurred but overall there were no significant changes. In the 6-week study amplification of the LH response to LHRH was found in both groups, the effect being significantly greater in the non-lactating women. Overall FSH responses were also significantly different in the two groups, being suppression in those lactating and amplification in those not lactating. The LH/FSH ratios following LHRH administration in the 6-week non-lactating study were similar to those seen in the early follicular phase in regularly menstruating subjects. The basal ratios in the lactating subjects were, however, significantly less than those seen in the non-lactating subjects both at 3 and 6 weeks. This difference was associated with the relative enhancement of LH release in non-lactating subjects and enhancement of FSH release in those lactating. Taken together the results indicate the presence of an intact negative feedback of oestrogen on gonadotrophin release in both groups being enhanced at 6 weeks post-partum in the lactating subjects; also in the lactating subjects at 6 weeks there was less amplification by oestrogen of the responsiveness of the anterior pituitary to LHRH. At 6 weeks, however, in the non-lactating group these responses were similar to those seen in normal regularly menstruating subjects. These dynamic endocrine studies suggest a possible hypothalamic- pituitary mechanism which may help to explain the delayed return of ovulatory cycles in lactating women.     

Effects of LHRH and long-acting LHRH on serum LH and FSH levels of healthy women

A comparison was made between the stimulatory effects of luteinizing hormone-releasing hormone (LHRH) and long acting luteinizing-releasing hormone (I.a. LHRH) on the gonadotropin secretion of normally menstruating women. The luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations were measured by RIA. The synthetic I.a. LHRH was found more potent than the parent hormone in terms of the magnitudes and durations of the LH and FSH responses. There was no close correlation between the initial gonadotropin values and the peak levels in normally menstruating women having basal LH and FSH values within the normal ranges.