The effect of long-term treatment with crude cotton seed oil on pituitary and testicular function in men

In a previous study, compensatory dysfunction of the Leydig cell was identified in men in whom spermatogenesis had failed to recover after gossypol treatment. In this study, LHRH- (100 micrograms i.v.) and hCG (3000 IU i.m.)-stimulation tests were conducted in four controls and in 45 men who had used crude cotton seed oil as their cooking oil. The patients were divided into two groups: group A--17 men with normospermia or oligospermia and group B--28 men who were azoospermic. The basal serum LH and FSH concentrations were within the normal range in group A, whereas those in group B were increased markedly. There was no significant difference in testosterone levels between the two groups, although the levels were significantly lower than in the controls. The response of LH and FSH to LHRH, and of testosterone to hCG stimulation, were within the normal range in group A, whereas in group B the response to the LHRH test was increased significantly while their response to the hCG test was reduced markedly. It was concluded that the functions of the pituitary and Leydig cells remained unchanged in group A after long-term use of crude cotton seed oil, and that once azoospermia has occurred, it is followed by total testicular failure as indicated by the responses to LHRH and hCG tests.     

Fertility and hormonal function in patients with a nonseminomatous tumor of the testis

Semen quality and serum testosterone, LH, and FSH levels were studied in 54 patients with a unilateral nonseminomatous tumor of the testis--14 before and 40 after orchiectomy. Semen analyses before and after orchiectomy gave essentially no different results: a poor semen quality was found in most men. The additional effect of a recent orchiectomy on semen quality was not demonstrable in the patients described here. Before orchiectomy, increased testosterone levels were found in patients with a beta-hCG-producing tumor. After orchiectomy serum testosterone levels were decreased, and LH and FSH levels increased. With beta-hCG-producing tumors FSH was suppressed after orchiectomy, and testosterone levels did not exceed those in patients with a tumor not producing beta-hCG. The results of semen analysis and of hormonal studies after orchiectomy suggest a dysfunction of the remaining "normal" testis. Diminished spermatogenesis and insufficient testosterone production by the Leydig cells clearly indicate anomalies already present before orchiectomy.     

Endocrine profiles and gonadotropin response to Gn-RH of men with testicular cancer

PURPOSE: To investigate the function of the hypothalamic-pituitary-testicular axis in testicular germ cell tumors, we evaluated gonadotropin responses to gonadotropin-releasing hormone (Gn-RH), semen quality, and serum levels of sex steroid hormones in patients with testicular cancer. PATIENTS AND METHODS: Basal serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), and human chorionic gonadotropin-beta (hCG-beta) were measured before and after high orchiectomy in 20 patients with germ cell tumors of the testicle (9 with seminoma and 11 with nonseminomatous tumor). Semen quality and basal serum levels of testosterone, free testosterone, and estradiol were measured before orchiectomy. The Gn-RH test was performed before orchiectomy in all patients and after orchiectomy in patients without detectable gonadotropin levels in pre-operative serum samples. Gonadotropin levels were measured at 0, 30, 60, 90, and 120 minutes after intravenous injection of 100 micrograms of luteinizing hormone-releasing hormone (LH-RH). RESULTS: Serum gonadotropin concentrations were not detectable in 6 of 8 (75%) men with hCG positive tumors or in 4 of 12 (33.3%) men with hCG negative tumors before orchiectomy. Before surgery, 10 men without detectable gonadotropin levels showed complete suppression of the LH and FSH responses to LH-RH and 10 men with detectable gonadotropin levels showed significant increases in the LH and FSH responses (p < 0.01) at 30 minutes. After surgery, the Gn-RH test was performed in 9 men without detectable gonadotropin levels prior to surgery. Seven of these 9 men exhibited significant increases in the LH and FSH responses (p < 0.01) at 30 minutes while no response to LH-RH before or after surgery was seen in 2 men with detectable serum hCG-beta. We observed a significantly lower sperm density (median 7.5 x 10(6)/ml, range 0.4 to 17.8) in men with hCG positive tumors than in men with hCG negative tumors (median 33 x 10(6)/ml, range 0 to 103) (p < 0.002). Although testosterone levels did not differ significantly in men with hCG positive tumors and men with hCG negative tumors, free testosterone levels were significantly higher in men with hCG positive tumors (median 28.4 ng/ml, range 8.5 to 39.8) compared with men with hCG negative tumors (median 18.7 ng/ml, range 4.9 to 24.1) (p < 0.002). Estradiol levels were significantly increased in men with hCG positive tumors (median 44 pg/ml, range 26 to 110) compared with men with hCG negative tumors (median 33.5 pg/ml, range 10 to 87) (p = 0.002). CONCLUSION: The present findings indicate that serum hCG producing testicular cancers are associated with a complete suppression of the gonadotropin response to Gn-RH at the pituitary level, resulting in an inhibition of LH and FSH secretion, and also that serum hCG secreted by testicular cancers may suppresses spermatogenesis and may stimulate androgen and estradiol production by the testes. Since suppressed serum gonadotoropin levels are found in men with hCG non-producing testicular cancers, other factors derived from the tumor may cause downregulation of the gonadotropin response to Gn-RH.     

醋酸棉酚对男子垂体－性腺轴功能的影响

报道２２例长期停服棉酚男子性激素的水平及其对ＬＨＲＨ和ｈＣＧ刺激的反应。２２例中，１１例生精功能未恢复者（无精子症组）的ＦＳＨ和ＬＨ基础值及其对ＬＨＲＨ刺激反应均显著高于正常对照组（１１例），而睾酮（Ｔ）基础值和Ｔ／ＬＨ比值及Ｔ对ｈＣＧ刺激反应显著低于正常对照组。生精功能恢复组（１１例）的ＦＳＨ基础值及其对ＬＨＲＨ刺激在应均显著高于正常对照组。但是，ＬＨ和Ｔ基础值及其对ＬＨＲＨ和ｈＣＧ刺激反应，二者差异不显著。这些结果说明，不适当的棉酚治疗所引起的永久无精子症者，全睾丸细胞受到严重损害，垂体－睾丸轴系功能调节发生紊乱；而适量的棉酚所引起的暂时无精子症，生精功能恢复以后，睾丸内分泌一般均正常     

PRETREATMENT FOLLICLE-STIMULATING HORMONE: A PROGNOSTIC SERUM MARKER OF SPERMATOGENESIS STATUS IN PATIENTS TREATED FOR GERM CELL CANCER

Purpose

We evaluate the use of pretreatment follicle-stimulating hormone (FSH) in patients with germ cell tumors as a prognostic serum marker of spermatogenesis after standard treatment. Additionally, Leydig cell function was investigated by estimation of luteinizing hormone (LH) and testosterone (T), and calculation of the T/LH ratio.

Materials and Methods

Serum FSH, LH and T were determined radioimmunologically associated with semen analyses in 20 patients with seminoma (pathological stages IA to IIB) after unilateral orchiectomy before and up to 24 months after infradiaphragmatic radiotherapy. Additionally, hormone analyses were performed in 18 patients with nonseminomatous germ cell tumor (pathological stages IIA to C) before and up to 36 months after standard cisplatin based chemotherapy.

Results

Seminoma patients undergoing radiotherapy were divided into 2 groups consisting of 12 patients with normal pretreatment serum FSH and 8 with elevated FSH reflecting spermatogenesis deficits even before treatment. Six months after irradiation a significant increase in FSH (p <0.01) associated with a decrease in sperm density was observed in both groups and 24 months after radiotherapy patients with initially normal FSH had significantly lower serum FSH (p <0.01) associated with higher sperm density than those with initially elevated FSH (p <0.01), indicating less impairment of Sertoli cell function. Comparable results were observed in chemotherapy treated germ cell tumor patients with initially normal (11) and elevated serum FSH (7), respectively, and 36 months after chemotherapy patients with initially normal FSH had significantly lower FSH concentrations than those with initially elevated FSH (p <0.01). Compensated impairment of Leydig cell function reflected by a subnormal T/LH ratio was evident before chemotherapy in 16.7% of patients increasing up to 41.2% 36 months after therapy. In contrast, 24 months after radiotherapy only 25% of seminoma patients showed a subnormal ratio reflecting less damage to the Leydig cells caused by irradiation.

Conclusions

Pretreatment FSH is a prognostic serum marker of spermatogenesis status of germ cell tumor patients receiving standard radiotherapy or chemotherapy. In contrast to seminoma patients after radiotherapy, impairment of Leydig cell function was evident in germ cell tumor patients after cisplatin based chemotherapy.     

Serum testosterone response to single injection of hCG ovine-LH and LHRH in male rats

A biphasic pattern of testosterone secretion in response to a single injection of 100 IU hCG has been observed in the rat. Serum testosterone increased from basal levels of 8.7 pL 3.1 ng/ml (mean pL SEM) to 23.0 pL 1.4 ng/ml within 2 h of hCG-stimulation and returned to control levels by 2 days. A second, delayed, but significant increase in serum testosterone occurred, reaching a peak of 24.6 pL 4.0 ng/ml at 3 days and declining to basal values at 5 days. To study this response further, lower doses of hCG were tried. Administration of 10 IU hCG produced a single peak of testosterone, which did not occur until 24 h. Differences in the serum testosterone response were related to the concentration of hCG measured in the serum after injection, as injection of 1 IU, which failed to increase serum hCG levels above detection, was also inadequate to increase serum testosterone. The response after stimulatin with 500 μg ovine-LH or 0.1–10.0 μg LHRH was also evaluated. Injection of 500 μg ovine-LH produced a significant rise in serum testosterone reaching a peak at 2 h of 25.2 pL 2.6 ng/ml and subsequently declining over the next 48 h to control levels where it remained for 5 days. Stimulation with doses of 0.1–10.0 μg LHRH produced rapid and short increases in serum LH concentration which induced peaks of testosterone up to 48.8 pL 14.1 ng/ml 1 h post injection. No secondary peak of testosterone followed. Failure of ovine-LH and LHRH to produce a second testosterone peak suggests that this response may be due to a re-stimulation of the Leydig cell by elevated levels of hCG which persist until the fourth day after injection.     

Effects of hCG stimulation after withdrawal of long-term oestrogen treatment in patients with prostate carcinoma

Testosterone depletion is the keystone for therapy of patients metastic prostatic carcinoma. Our objective was to investigate Leydig cell function and testosterone levels after withdrawal of long-term endocrine treatment in patients with prostatic carcinoma. Thirteen patients with prostatic carcinoma, previously treated with oestrogens for at least 4 y, were stimulated with 5000 IU human chorionic gonadotrophin (hCG). The stimulation was performed 3-6 y after cessation of the oestrogen therapy. Serum concentrations of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured before and 24 and 48 h after hCG stimulation. Before hCG stimulation all patients had low serum testosterone concentrations (mean 2.0+/-0.2 nmol/l) and 24 and 48 h after hCG stimulation the values had not significantly increased (mean 2.4+/-0.2 and 2.5+/-1.1 nmol/l, respectively). LH and FSH were within or above the normal range before but after hCG stimulation the values significantly increased. In conclusion, the study shows that the Leydig cells were unable to respond to hCG stimulation more than 3 y after cessation of oestrogen therapy. The Leydig cell function seems to be irreversibly impaired by long-term oestrogen treatment.     

Experimental cryptorchidism in the adult mouse: II. A hormonal study

Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels and secretory capacity of the in vitro stimulated testis were determined in control and bilateral cryptorchid mice after 7, 14, 21, and 28 days. In a separate study, serum FSH, LH, and testosterone levels were measured in unilateral and bilateral cryptorchid, hemicastrate, and bilaterally castrate adult mice after 28 days of treatment. Serum FSH levels were significantly increased in bilaterally cryptorchid mice compared to controls (0 days) at 7, 14, 21, and 28 days, but serum LH and testosterone levels did not change. At 28 days, the elevated serum FSH levels in the unilateral and bilateral cryptorchid mice were not different than those in hemicastrate mice. However, the FSH levels in bilaterally castrate mice after 28 days were significantly higher than all other groups. Serum LH and testosterone levels were significantly different only in the bilaterally castrate group, compared to control levels. Both the normal and cryptorchid testes of all ages studied were capable of producing equal levels of testosterone in vitro, both basally and with a human chorionic gonadotropin (hCG) dose of 700 mIU/ml (maximum stimulatory dose for both the normal and the 28 day cryptorchid testes). Changes that occur in mice with experimentally induced cryptorchidism are not identical to those seen in the rat. Serum FSH levels increase, but no changes occur in serum LH and testosterone levels. Additionally, a cryptorchid mouse testis is not hyperresponsive to hCG stimulation in vitro.     

The impact of simple orchiectomy on semen quality and endocrine parameters in postpubertal cryptorchid men

Purpose

The main objectives of this retrospective cohort study were to evaluate reproductive endocrine and semen profiles before and after simple orchiectomy in patients with unilateral postpubertal cryptorchidism and to investigate the relationship between hormone levels and histopathology of the removed testis.

Methods

We evaluated 40 adult males who were admitted to our clinic, between 2001 and 2007, with unilateral undescended testis. Right orchiectomy was performed in 27 patients and left orchiectomy in 13. Semen analysis, serum inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were examined in before and 3?months after orchiectomy. Orchiectomy materials were evaluated histopathologically.

Results

Semen parameters, as well as testosterone and LH levels, did not change in any histopathological subgroups in the postoperative follow-up. In patients with maturation arrest, mean serum inhibin B level statistically significantly decreased from 160.9 to 83.5?pg/ml, and mean FSH level significantly increased from 4.8 to 7.6?mIU/ml after orchiectomy (p value, 0.008 and 0.008, respectively). Though, the levels were still within the normal range of the two hormones.

Conclusions

Simple orchiectomy does not have any effect on semen parameters and testosterone level in patients with postpubertal cryptorchidism. The change in inhibin B and FSH levels after orchiectomy in patients with maturation arrest is not clinically significant.     

Pituitary Gonadal Function in Infertile Men with Varicocele

Infertile men with varicocele or idiopathic infertility were compared with a control group. Spermocytograms were taken and the following radioimmunological plasma analyses carried out: testosterone, FSH and LH before and after 50 micrograms LRH, Prolactin (PRL) before and after 200 micrograms TRH; in addition, 8 patients with varicoceles and 3 controls received LRH intravenously (0.4 microgram/min.) for 4 hours. The binding of [125I] human chorionic gonadotrophin (hCG) to testicular tissue obtained by biopsy from 10 infertile men was also investigated. Of the parameters studied, no differences were found between the unilateral or bilateral varicoceles. In the two groups of infertile men, sperm motility and percentage normal forms were similar and significantly lower than in controls. As compared to the controls, in the groups of infertile men, basal LH and testosterone levels were no different but basal FSH levels was increased, basal PRL was higher (p less than 0.05) in the varicocele group. Responses of the LH, FSH and PRL to LRH and TRH stimulations were generally higher in infertile men than in controls. As compared to the idiopathic infertile men, testosterone levels and responses of plasma FSH to LRH injection were lower in varicocele group. Moreover, in infertile men with varicocele, age was correlated negatively with sperm motility and testosterone level and it was correlated positively with LH response to LRH injection. For each patient, testicular tissue was able to specifically bind [125I]hCG, but in some cases of varicoceles, hCG binding capacity was different in the two testes and seemed higher than that observed in men with obstructive azoospermia. These results suggest: 1) dysfunction in both spermatogenesis and Leydig cells with a compensatory hyperfunction of the pituitary gland in infertile men with varicocele; 2) worsening in Leydig cells and tubular lesions with longer duration of varicocele; and 3) absence of any gross abnormality in hCG binding to its specific receptors in the testis of men with varicocele. These data suggest varicoceles may play a causal role in infertility.     

Early effects of hCG on human testicular cyclic AMP content, protein kinase activity, in-vitro progesterone conversion and the serum concentrations of testosterone and oestradiol

Ten infertile men underwent testicular biopsy. Cyclic AMP concentration and cAMP-dependent protein kinase activity were determined in biopsies obtained before, and at 3, 10, 20 and 30 min after an intravenous injection of hCG (1500-5000 IU). The in-vitro conversion of progesterone by testicular tissue, and the serum concentrations of testosterone and oestradiol were then studied before and at 30 min after hCG injection. Intravenous injection of hCG induced a rapid increase in cAMP concentration and in the activity of cAMP-dependent protein kinase. The kinetics of this response indicated that cAMP and cAMP-dependent protein kinase mediate hCG effects on the human testis, presumably via effects on the Leydig cells. No stimulatory effect on steroid conversion in vitro or on the serum concentrations of testosterone and oestradiol were seen after 30 min.     

Pituitary-testicular reserve in men with low serum testosterone and normal serum luteinizing hormone

Men with low serum testosterone levels who do not have elevated serum LH levels are generally thought to have hypothalamic-pituitary dysfunction. To evaluate this concept, seven men with a combination of low serum testosterone and normal serum LH underwent standard tests of hypothalamic-pituitary-testicular reserve. Pituitary reserve, tested with LHRH, showed exaggerated responses in two subjects, low-normal responses in one subject, and normal responses in the remaining four. Testing of hypothalamic-pituitary reserve with clomiphene showed normal gonadotropin responses in six subjects and blunted response in one (the same subject with the low LHRH response). Direct stimulation with hCG showed normal percentage increases in testosterone but low absolute levels, comparable to responses in patients with Klinefelter's syndrome. However, 17-OH-progresterone responses to hCG were lower in these subjects than in either controls or subjects with Klinefelter's syndrome. During follow-up, one subject developed frank primary testicular failure. It was concluded that men with low serum testosterone but normal serum LH are a heterogeneous group, and this pattern occasionally reflects early primary testicular failure rather than hypothalamic-pituitary dysfunction. Standard tests of pituitary-testicular reserve are generally not useful in defining abnormal hormonal output, although measurement of the 17-OH-progesterone response to hCG may improve their diagnostic utility.     

Hormonal and seminal evaluation of Leydig cell tumour patients before and after orchiectomy

Seven patients (aged 25-38 years) were admitted because of mono- or bilateral gynaecomastia. Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, testosterone, 17-beta-estradiol, delta4-androstenedione, dehydropiandrosterone sulphate (DHEA-S) and 17-OH-progesterone were determined and semen analysis was carried out. FSH and LH levels were also measured after acute LH-RH administration (100 microg intravenously), and testosterone and 17-beta-estradiol were also evaluated after acute human chorionic gonadotrophin (hCG) administration (5000 IU intramuscularly). Testicular echography demonstrated the presence of a solid hypoechoic tumour. Therefore all patients were submitted to hemicastration by orchidofuniculotomy and a benign Leydig cell tumour was diagnosed in the removed testes. Hormonal and semen evaluations were repeated 3, 6, 9 and 12 months after surgery. The data before and after surgery were compared with a control group of 10 age-matched males. Before surgery, patients showed low FSH basal plasma levels; high levels of 17-beta-estradiol and low testosterone levels similar to those after hCG administration. A dyspermia was observed. Unilateral orchidectomy eliminated the autonomous secretion of oestrogen(s) so an increase of LH, FSH and testosterone levels, together with an improvement of spermatogenesis, were obtained.     

A hCG-secreting testicular seminoma revealed by male infertility: mechanism of hCG-evoked endocrine disturbances

Summary. We report a case of a hCG-producing testicular seminoma revealed by a male infertility due to oligozoospermia. No palpable tumour was found at clinical examination and the diagnosis was established on hormonal data and the echography of the testis. The endocrine patterns associated high levels of β-hCG and 17β-oestradiol contrasting with low levels of LH and FSH and normal levels of testosterone. Immuno-histochemical studies confirmed the ectopic production of hCG. Histological findings and the evolution of hormonal parameters suggested that hyperoestradiolaemia was probably the consequence of a hCG-evoked Leydig cells hyperplasia involving a paracrine mechanism. In fact, after removal of the tumour, a dramatic decrease of plasma sex steroid levels was observed before recovery of normal testicular endocrine and exocrine functions.     

Gonadal function and fertility in patients with bilateral testicular germ cell malignancy

OBJECTIVE: To evaluate gonadal function and fertility in patients with bilateral testicular cancer (TC). METHODS: In 1999, 63 patients with bilateral invasive TC or carcinoma in situ (CIS) in the contralateral testis completed a mailed questionnaire evaluating their fatherhood (Cases). Their gonadal function had also been assessed after the first orchiectomy for TC before further treatment.The results were compared with those from 174 patients with unilateral TC (Controls). RESULTS: In Cases the post-orchiectomy serum levels of FSH and LH were above those of the Controls (p<0.001). Serum testosterone was similar, whereas sperm concentrations were lower in Cases (p<0.001). In Cases with metachronous invasive TC the level of serum FSH was associated with the interval between the two diagnoses. After the first orchiectomy, 10 of 25 Cases (40%) initiated a pregnancy, in 4 Cases by assisted fertilization. In the Control group 74% of the patients who attempted fatherhood succeeded (p=0.002). CONCLUSIONS: After unilateral orchiectomy for TC elevated serum FSH and/or oligospermia represent a high-risk factor of metachronous bilateral TC or synchronous CIS. At least one-third of these patients attempting fatherhood are successful after the first orchiectomy. Assisted fertilization is often necessary and the overall paternity rate is below that of patients with unilateral TC.     

The gonadotropin response to synthetic gonadotropin releasing factor in patients with testicular cancer

The response of LH and FSH to synthetic gonadotropin releasing factor (GRF) was investigated in 19 patients with malignant germ cell cancers of the testicle prior to radical orchiectomy. The study showed: 1. Patients with circulating beta-HCG presented with increased plasma levels of oestradiol. Base line FSH and response to GRF were significantly decreased. 2. In patients without detectable beta-HCG plasma concentrations of oestradiol and testosterone were within the normal ranges as compared to healthy age matched controls. Base line levels of FSH and LH were increased and an exaggerated response to GRF was observed. From the results of this study it can be concluded that hypergonadotropic dysfunction of pituitary-gonadal axis exists in patients with testicular cancer of germ cell origin. Beta-HCG production by tumour tissue results in hyperoestrogenism and interferes with the pituitary-gonadal axis in terms of inhibition of pituitary gonadotropin release.     

Aminoglutethimide in advanced prostatic carcinoma

We have treated 34 patients with advanced prostate cancer, resistant to orchiectomy or oestrogen therapy, with aminoglutethimide. Seven patients (21%) showed improvement in pain and performance status for prolonged periods. By NPCP criteria six patients had stable disease and one had partial tumour response. Six of these patients remained on oestrogen therapy. Suppressed gonadotrophin levels (FSH and LH), despite orchiectomy, correlated strongly with benefit from aminoglutethimide. No relationships between response to treatment and changes in serum testosterone, dehydroepiandrosterone, oestradiol or prolactin were found. Six patients had side effects requiring cessation of therapy. A further 27 patients developed less severe toxicity. Despite its toxicity, these results show that aminoglutethimide has a role in the management of advanced prostatic cancer resistant to primary hormonal manipulation.     

Inhibin secretion is influenced by Ley dig cells: evidence from studies using the cytotoxin ethane dimethane sulphonate (EDS)

Adult male rats given a single intraperitoneal injection of the Leydig cell cytotoxin ethane dimethane sulphonate (EDS) show a significant decrease in testosterone from 7 to 14 days, and elevation of serum FSH and LH levels commencing 7 days after treatment, returning to normal at 28 days for LH and 49 days for FSH. A significant rise in serum inhibin levels was seen at day 14 after EDS treatment with levels returning to normal at day 49. In a second series of experiments, silastic implants of testosterone, either 2.5 cm or 22.5 cm in length, were introduced subcutaneously into adult male rats which were treated with EDS 10 days later. Both doses of testosterone suppressed basal LH levels but did not significantly change FSH levels. The rise in FSH and LH levels seen in normal rats after EDS treatment did not occur in either group of testosterone-implanted rats. However, serum inhibin levels rose significantly in both groups after EDS treatment, suggesting that the rise in serum inhibin levels was not due to stimulation arising from the increase in FSH levels after EDS treatment. The data suggest that the rise in serum inhibin levels after EDS treatment is linked to destruction of the Leydig cells through mechanisms that require further investigation.     

The physiological significance of pulsatile LHRH secretion in man: gonadotrophin responses to physiological doses of pulsatile versus continuous LHRH administration

This study tested whether pulsatile LHRH stimulation of the pituitary is required for normal gonadotrophin secretion in man. Four men with idiopathic hypogonadotrophic hypogonadism (IHH) and presumed endogenous LHRH deficiency were taken off all hormonal replacement for 5-6 weeks, then 5 micrograms LHRH was administered every 2 h for 1 week in order to prime pituitary gonadotrophin responsiveness. A physiological dose of LHRH (10 micrograms every 2 h) was then administered in both pulsatile and continuous regimens, in varying order, to each man. Pulsatile LHRH was capable of stimulating LH (as measured by bioassay) and FSH secretion, while continuous administration of LHRH was not. Serum LH, measured by RIA and bioassay, and FSH and free alpha-subunit levels, measured by RIA, increased significantly (P less than 0.05) over pretreatment levels during pulsatile LHRH administration. In contrast, bioactive LH and immunoactive FSH did not change significantly compared to pretreatment values during continuous infusion of the same total LHRH dose, although immunoactive LH and free alpha-subunit levels did increase significantly (P less than 0.05). The ratio of LH bioactivity to immunoactivity was significantly lower during the continuous compared to pulsatile LHRH regimen (P less than 0.001). Similar serum LHRH levels were achieved during pulsatile and continuous infusions. Serum testosterone and oestradiol levels did not increase significantly from pretreatment levels during either regimen of LHRH administration. It is concluded that a pulsatile LHRH signal pattern is essential for normal pituitary gonadotrophin secretion in men with IHH. Continuous infusion of a physiological dose of LHRH, which produced serum LHRH levels which were indistinguishable from those found during pulsatile administration, failed to stimulate FSH or bioactive LH secretion.     

Effect of clomiphene treatment on the human testicular response to a single dose of hCG

The effect of antioestrogen treatment on the human testicular response to hCG was investigated in 17 adult men to further clarify the role of endogenous oestradiol in the regulation of testicular steroidogenesis. Clomiphene citrate was administered in 2 different modes. Group 1 (n = 8) was treated for 6 days (100 mg of the antioestrogen once a day) and a single dose of hCG (5000 IU im) was given at the beginning of the experiment. In group 2 (n = 9), the treatment was started 7 days prior to the hCG injection and was continued for additional 6 days. In both groups peripheral blood samples were collected up to 6 days after hCG, and the sera were analysed for FSH, prolactin and 8 steroids. In group 1, the steroidogenic response was identical to that found previously in untreated men. In group 2, the 7-day treatment with clomiphene citrate led to elevated serum concentrations of LH, FSH, pregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, 5α-dihydrotestosterone and oestradiol. When compared with these elevated values, the responses of serum 17-hydroxyprogesterone. dehydroepiandrosterone, androstenedione and testosterone to hCG were diminished. The ratios of the steroid concentrations support previous reports that hCG-induced inhibition of 17-hydroxylase, 17–20 desmolase and 3β-hydroxysteroid dehydrogenase-Δ^4–5 isomerase is decreased during antioestrogen administration. This further substantiates the idea of a central role for endogenous testicular oestradiol in the mediation of steroidogenic lesions following acute large doses of hCG.