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.     

Interaction of Inhibin and Estrogens on Basal and LRH-stimulated Gonadotropin Levels

Summary: In order to study the action of estrogens and inhibin and their interaction with gonadotropin secretion in men, we measured basal and LRH-stimulated gonadotropin secretion before and after six weeks' administration of tamoxifen in two groups of men. A) Six men with impaired spermatogenesis with basal levels of FSH, LH, testosterone and estradiol within the range of reference values in our laboratory. B) Six men with severely impaired spermatogenesis. LH, testosterone and estradiol levels were within reference values, whereas FSH was at least 100% above the upper limit of reference values. Mean testosterone and estradiol levels were not different in either groups. Inhibin levels were presumed to be normal in group A and decreased in group B. Although within reference values, basal LH levels in group B were slightly but significantly higher than in group A. The response of LH to LRH in group B exceeded that of group A. This suggests that inhibin has a slightly inhibitory effect on basal LH and even more so on LRH-induced LH secretion. After tamoxifen administration basal FSH levels rose far more in group B than in group A. The LRH-induced LH release increased in both groups, the LRH-stimulated FSH release, however, increased only in group A. We conclude that estrogens and inhibin have a strongly synergistic negative feedback action on basal FSH secretion, and to a limited extent on basal LH secretion. In the presumed presence of inhibin (group A) the FSH additionally synthesized through the action of anti-estrogens, can be released by LRH administration, whereas FSH is probably spontaneously released in the presumed deficiency of inhibin (group B). With LH this phenomenon is less obvious. Zusammenfassung: Die Interaktion von Inhibin mit Östrogenen und deren Einfluß auf die basalen und von LRH stimulierten Gonadotropinspiegel Ziel dieser Untersuchung war es, die Wirkung von Östrogenen und Inhibin und ihre Wechselbeziehung auf die Gonadotropinsekretion beim Mann zu überprüfen. Dazu wurden die basalen und die von LRH stimulierten Gonadotropinspiegel vor und nach sechswöchiger Behandlung mit Tamoxifen bei 2 Gruppen von Männern gemessen. A) Sechs Männer mit beeinträchtigter Spermatogenese: die basalen Spiegel von FSH, LH, Testosteron und Östradiol waren im Normalbereich unseres Labors. B) Sechs Männer mit stark gestörter Spermatogenese: LH, Testosteron und Östradiol waren im Normalbereich, während FSH mindstens 100% über der Obergrenze lag. Die Mittelwerte der Testosteron- und Östradiolspiegel waren in den beiden Gruppen nicht unterschiedlich. Es wurde angenommen, daß die Inhibinspiegel normal waren in Gruppe A und herabgesetzt in Gruppe B. Die basalen LH-Spiegel in Gruppe B, obwohl noch im Normalbereich, waren höher als in Gruppe A. Die Reaktion von LH auf LRH in Gruppe B übertraf die der Gruppe A. Das könnte darauf hinweisen, daß Inhibin einen geringen hemmenden Effekt aut die basale und einen stärkeren Effekt auf die von LRH induzierte LH-Sekretion hat. Nach Tamoxifengaben stiegen die basalen FSH-Werte in Gruppe B weitaus höher als in Gruppe A. Die von LRH induzierte Freisetzung von LH stieg in beiden Gruppen; die von LRH stimulierte FSH-Sekretion dagegen nur in Gruppe A. Wir schließen hieraus, daß Östrogene und Inhibin einen starken synergistischen negativen Feedback ausüben auf die basale FSH-Sekretion und gewissermaßen auf die basale LH-Sekretion. In der vorausgesetzten Anwesenheit von Inhibin (Gruppe A) kann das durch die Anti-Östrogene zusätzlich synthetisierte FSH freigesetzt werden von LRH, während FSH möglicherweise spontan freigesetzt wird bei einer mangelhaften Inhibinproduktion (Gruppe B). Für LH ist dieses Phänomen weniger deutlich.     

Leydig cell function in adolescent boys with varicoceles

The incidence of varicoceles in adolescent boys ranges from 5% to 19.5%. We studied five adolescent boys aged 17 to 20 years with visible left-sided varicoceles. All of them had public hair and testicular volumes between 20 to 25 mL and had achieved stage V of pubertal development. Serum gonadotropin response to the intravenous administration of 100 micrograms of gonadotropin-releasing hormone (GnRH) and testosterone response to the administration of 2,000 IU human chorionic gonadotropin (hCG) daily for 3 days before and 3 months after varicocelectomy were measured. Basal levels of both gonadotropins were in the pubertal range, and there was no significant difference between serum levels before and after varicocelectomy. Both gonadotropins, however, showed increased responses to the administration of GnRH (luteinizing hormone [LH]: basal, 12.0 +/- 5.1 mIU/mL; peak, 105.0 +/- 36.0 mIU/mL; follicle-stimulating hormone [FSH]: basal, 11.6 +/- 4.2 mIU/mL, peak, 60.0 +/- 18.0 mIU/ml) that decreased after varicocelectomy (LH: basal, 14.3 +/- 6.0 mIU/mL; peak, 58.6 +/- 12.0 mIU/mL; FSH: basal, 6.8 +/- 4.6 mIU/mL; peak, 38.0 +/- 8.1 mIU/mL). Serum testosterone response to hCG was also significantly improved by varicocelectomy (testosterone peak: before, 780 +/- 210 ng/dL; after, 1850 +/- 170 ng/dL). Testicular biopsy specimens showed no histologic abnormalities and normal spermatogenesis. Endocrine evaluation in adolescent boys with varicoceles could detect an early Leydig cell dysfunction that could be corrected by varicocelectomy.     

Prolactin Secretion in Adolescent Boys with Hypogonadism

Basal and TRH stimulated plasma prolactin levels were determined in 24 pubertal boys with hypogonadism (Primary: n = 10; secondary: n = 4; tertiary (hypothalamic): n = 10) and controls matched for pubertal stage (n = 12). The differentiation between secondary and tertiary hypogonadism was made with the help of a prolonged LRH test. The TRH test was performed by injecting 200 mcg i.v. in one bolus and taking plasma samples at 0, 15, 30, 60 and 90 minutes. No statistically significant differences were found between any of the groups. It is concluded that determination of basal or TRH stimulated prolactin does not contribute to clarify the etiology of hypogonadism or to determine the grade of damage or dysfunction in the hypogonadic testes.     

Three cases of Klinefelter syndrome in childhood--endocrinological and gonadal changes in puberty

Three children at the ages of 4, 10 and 12 years, with external genital malformation, were diagnosed to be with the Klinefelter syndrome by chromosome analysis. To clarify the pubertal changes in this syndrome, all of them were studied for physical and endocrinological examinations and two underwent testicular biopsy. Before puberty any remarkable abnormality were not observed in the hypothalamus-pituitary-gonadal axis and in the physical status. After the onset of puberty they started showing increases of the basal levels of plasma FSH and LH with over-response to LH-RH stimulation test. During the period of this study the levels of plasma testosterone were in the normal range and increased gradually with age. One boy showed a transient high level of plasma testosterone at early puberty. The reactions of plasma testosterone to HCG stimulation of all cases showed the normal pattern. The histological examination of the testis revealed that the number of spermatogonia was reduced in both cases compared with that of normal boys reported by Mancini et al. These findings indicate that most endocrinological and histological abnormalities in adult Klinefelter syndrome occur after the onset of puberty. These changes may be induced at puberty by hypergonadotrophic condition which result from slightly impaired testicular function which is present before puberty.     

Estrogens in the Feedback Regulation of Gonadotropin Secretion in Men: Effects of Administration of Estrogen to Agonadal Subjects and the Antiestrogen Tamoxifen and the Aromatase Inhibitor δ''-Testolactone to Eugonadal Subjects

To elucidate the specific role of estrogens in the feedback regulation of gonadotropin secretion in men, basal and LRH-stimulated gonadotropin levels were studied in: Six agonadal subjects Six agonadal subjects continuously treated with 50 micrograms ethinylestradiol Six eugonadal subjects, treated with the aromatase inhibitor delta'-testolactone, which induced a reduction of estrogen levels, independently of testosterone. Further, to determine whether estrogens exert differential effects in time on LH and FSH secretion, the anti-estrogen tamoxifen was administered to: Six eugonadal subjects for two weeks and Six eugonadal subjects for six weeks. It was found that estrogens have a strong suppressive effect on both LH and FSH secretion. However, changes in estrogen levels and blocking of estrogen receptors are followed more rapidly by FSH than LH. Estrogens affect LRH-induced LH release more than basal LH levels; basal and LRH-stimulated FSH are approximately equally influenced. Basal and LRH-induced LH secretion are known to be more dependent upon previous LRH stimulation than FSH secretion. Since FSH followed changes of estrogens more rapidly than LH did, we postulate that the negative feedback action of estrogens on: LH secretion is predominantly exerted at the level of the hypothalamus, through inhibition of LRH secretion FSH secretion predominantly at the level of the pituitary through a direct action on the gonadotroph.     

Regulation of interstitial cell function by seminiferous tubules in intact and cryptorchid rats

The effects of experimental cryptorchidism on seminiferous tubule secretions and interstitial cell testosterone production were studied in vitro. Spent media obtained from incubations of seminiferous tubules (SMST) from cryptorchid rats caused a significant increase in testosterone production when added to interstitial cells isolated from intact rats. The previously noticed inhibitory activity of the SMST from stages VIII–XI of the sperma-togenic epithelial cycle gradually disappeared after the induction of experimental cryptorchidism. SMST obtained from both sham-operated or cryptorchid rats stimulated basal testosterone production when added to interstitial cells from cryptrochid rats. SMST from rats had been cryptorchid for 7, 14 and 28 days stimulated testosterone production when added to interstitial cells prepared from intact animals. Seminiferous tubules from cryptorchid rats therefore appear to be the source of a heat stable, trypsin-resistant factor with an apparent molecular weight of between 5000 and 10 000 daltons which stimulates testosterone production when added to interstitial cells in vitro. Its activity could not be blocked by an LRH antagonist. This factor enhances both basal and LH-stimulated secretion of testosterone in contrast to the inhibitory activity which involves only a partial blockade of LH-dependent steroidogenesis.     

Male fertility in long-term survivors of childhood acute lymphoblastic leukaemia

To study long-term testicular function following the treatment of acute lymphoblastic leukaemia (ALL) in childhood, 37 young adult males were assessed at two separate time points. The initial assessment was made by a wedge testicular biopsy after completion of treatment (median 9.7 years; range 4.1-16.3 years) and the subsequent assessment (median 18.6 years; range 15.4-26.8 years) consisted of the clinical examination of pubertal stage, measurement of serum gonadotrophins and testosterone and, in 19 patients, semen analysis. All 37 men completed pubertal development normally and had a testosterone concentration within the normal adult range. Six men showed evidence of severe damage to the seminiferous epithelium, five were azoospermic and one, who did not provide semen for analysis, had a reduced mean testicular volume (11 mls; normal greater than or equal to 15 mls) and a raised basal FSH level (13 UI 1-1; normal less than or equal to 6 IU 1-1). All six men with germ-cell damage had received either cyclophosphamide or both cyclophosphamide and cytosine arabinoside as part of their chemotherapy regimen. Approximately 10.7 years earlier all 37 men had undergone a testicular biopsy after completion of their chemotherapy. Morphological damage to the seminiferous epithelium had been calculated by estimating the tubular fertility index (TFI), which is the percentage of seminiferous tubules containing identifiable spermatogonia (age-matched normal = 100%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Testicular function following cyclophosphamide treatment for childhood nephrotic syndrome: long-term follow-up study

Testicular function of 17 males treated in childhood or adolescence for nephrotic syndrome (NS) with cyclophosphamide (CY) for a mean time of 240 days (mean total dosage of 16.4 g or 641 mg/kg body weight) was evaluated at a mean time of 11.8 years after treatment. Five were azoopsermic, 1 oligospermic, and 11 normospermic. There was a significant inverse correlation of sperm density with CY dosage and duration of treatment. All patients had undergone normal pubertal development and had normal sexual characteristics. Both basal and gonadotropin-releasing hormone-stimulated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations were significantly raised in oligo- and azoospermic patients. Raised basal and peak FSH and LH concentrations in normospermic patients with a sperm count of less than 40×10⁶/ml were in keeping with impairment of two testicular components. However, mean basal plasma testosterone levels and mean peak plasma testosterone responses to human chrionic gonadotropin (HCG) did not differ significantly between patients and controls. Although LH responses to gonadotropin-releasing hormone suggested compensated Leydig cell failure in patients with testicular tubular damage, secretory reserve capacity of these cells, estimated by a HCG stimulation test, was preserved. Further follow-up is required to ascertain whether in these patients Leydig cell failure will develop with time.     

Effects of Dexamethasone and Testosterone Propionate on LH Response to Gonadoliberin (LRH) in Young Post-Pubertal Bulls

LH and testosterone responses to gonadoliberin (LRH) were studied after previous dexamethasone and testosterone propionate combined treatment (treated group) compared with a single dexamethasone previous treatment (control group) in 12 Montbéliarde bulls aged 15 months. This experiment was performed on two occaisions 6 months apart according to the same schedule. They included each time 6 bulls, treated with intramuscular injections of 400 mg testosterone propionate and 6 hours later 0.25 mg gonadoliberin together with the other 3 bulls. Testosterone propionate did not influence the mean LH response to gonadoliberin although mean testosterone levels before gonadoliberin injection was very low in the controls. These data suggest that (1) the previously reported depressing effect of dexamethasone on LH is not mediated by the low peripheral testosterone level and (2) under the conditions of this study, there is no short term effect of testosterone at the pituitary level.     

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.     

Influence of hypothyroidism on epididymal enzymes involved in carbohydrate metabolism Studies in pubertal and adult rats

The influence of thyroidectomy on key epididymal enzymes of the Embden-Meyerhof and pentose phosphate pathway have been studied in pubertal and adult animals in relation to the serum hormone profile. Age related differences in the response of epididymal segments were observed with respect to hexokinase activity, although the other 2 key enzymes of the Embden-Meyerhof pathway (6-PFK and PK) were suppressed in all regions of the epididymis in both pubertal and adult rats. The enzymes involved in the pentose phosphate pathway (G-6-PDH and 6-PGDH) remained unaltered. The serum hormone profile revealed that while FSH and testosterone titres were reduced, LH and Prl were unaltered. Replacement of T4 in thyroidectomized animals maintained serum hormone levels and the activities of the enzymes studied at control levels. It is inferred that thyroid hormones may be one part of a complex mechanism that controls carbohydrate metabolism in the epididymis.     

Evidence for the role of androgens in the feedback control of gonadotrophin secretion in the human female

The effect of androgens on the luteinizing hormone (LH) response to LH-releasing hormone (LH-RH) is fairly well documented. However, the evidence concerning the effect on follicle-stimulating hormone (FSH) is less convincing and clear-cut. We administered LH-RH to a patient with an androgen-producing adrenal tumour both before and after removal of the tumour. Before operation, testosterone levels were elevated and oestradiol levels reduced. There was no response of either LH or FSH levels to LH-RH on two separate occasions. Postoperatively LH and FSH values rose sharply, to 404% and 170% above basal levels respectively. The data suggest that androgens do play a role in the feedback control of both LH and FSH secretion.     

ALTERATION OF THE HYPOTHALAMUS-PITUITARY-TESTIS AXIS IN OLIGOZOOSPERMIC MEN WITH NORMAL GONADOTROPIN LEVELS

Background:
Serum basal hormone levels such as lutenizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone, which is important to regulate testicular function, do not necessarily indicate the normal integrity of the hypothalamic-pituitary-testicular axis and the static measurement is not enough to detect the endocrine disorder. The dynamic measurement of gonadal hormone by GnRH test is considered to be more helpful to understanding the endocrine regulation of spermatogenesis. In this study, we performed GnRH test in oligozoospermic patients with normal levels of LH and FSH to examine the subtle alteration of hypothalamic-pituitary-testis axis.
Methods:
GnRH test was performed in 41 patients with oligozoospermia and normal gonadal hormone levels.
Results:
The responses of LH and/or FSH were excessive in most patients in spite of their normal gonadotropin levels. The patients with sperm concentration < 10 ± 10⁶/ml had significantly higher peak levels of both LH and FSH than did those with sperm concentration > 10 ± 10⁶/ml. In the patients with normal peak levels of both LH and FSH, sperm concentration was significantly higher than those with exceeded peak levels of FSH and/or LH after GnRH test. No significant differences were observed in estradiol, testosterone, free testosterone, or prolactin (PRL) levels between patients with normal responses and abnormal responses of LH and/or FSH.
Conclusions:
The feedback control of gonadotropin release from testis was worse in more severely oligozoospermic patients, although the precise mechanism of feed back still remains unknown.     

Effect of urinary bilharzial infection on male pubertal development and endocrine functions

One hundred seventy-five males aged 9-20 years were selected. The subjects comprised two groups; controls and patients infected with urinary bilharziasis not associated with any other parasite. Pubertal development was assessed. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and progesterone were determined by radioimmunoassay procedure. Delay in pubertal development was evident in the normal control group as indicated by higher chronological age mean values at the various stages as compared to other world norms. Urinary bilharziasis exaggerated the delay in pubertal development as compared to that in the control group. In relation to the control group, the group with urinary bilharziasis had higher levels of serum FSH and LH, which were significant only at stages III and IV. No significant difference was noted between the two groups for serum testosterone and progesterone levels, except for the high progesterone mean value at stage V in the group with urinary bilharziasis.     

Chronic immobilization-induced stress increases plasma testosterone and delays testicular maturation in pubertal rats

We investigated whether chronic stress, applied from prepuberty to early puberty, interferes with the spermatogenic and androgenic testicular functions. Male pubertal rats (40 days old) were immobilized 6 h per day for 15 days. Plasma concentrations of corticosterone, prolactin and testosterone were significantly augmented following immobilization, whereas plasma luteinizing hormone decreased and follicle-stimulating hormone was not altered. Acute immobilization (5 min) increased prolactin and testosterone levels in control rats but caused a significantly higher increase in these hormones when superimposed on chronic stress. A lower extent of testicular maturation was observed in pubertal rats immobilized from prepuberty.     

Influence of LRH on gonadotrophin and testosterone levels in the foetal male rat

Gonadotrophin and testosterone levels were measured in male foetal rats at the 21st day of gestation 30 min following administration of LRH. The releasing hormone was administered by 3 different routes: subcutaneously as a single injection to the pregnant rat; subcutaneously as 12 times repeated injection to the pregnant rat from 16th-21st day of gestation; direct injection into the amniotic cavity. Three different doses of 1, 5, and 10 microgram/kg were used. The single administration to the dam was without effect. Repeated doses resulted in a significant dose-dependent elevation of mean foetal LH: 163 ng/ml in the control animals and 133,256, and 363 ng/ml in the 1, 5, and 10 microgram/kg LRH group resp. Intra animal injections significantly increased FSH and LH levels, but only those of FSH were clearly dose-dependent. A mean of 390 ng/ml in the control group was observed, with 1 microgram/kg LRH FSH was elevated to 723 ng/ml, at 5 microgram/kg to 928 and at 10 microgram/kg to 1017 ng/ml. Testosterone levels were not significantly altered. Our results demonstrate that the pituitary of foetal rats is able to respond to LRH in the same manner as adult animals.     

Urinary phthalate excretion in 555 healthy Danish boys with and without pubertal gynaecomastia

Pubertal gynaecomastia is a clinical sign of an oestrogen-androgen imbalance, which occurs in 40-60% of adolescent Caucasian boys. In most cases no underlying endocrinopathy can be identified. A recent study reports higher plasma phthalate levels in Turkish boys with pubertal gynaecomastia. Therefore, we asked whether there was an association between concurrent measures of urinary phthalate metabolites and pubertal timing as well as the presence of gynaecomastia in otherwise healthy boys. We studied a total of 555 healthy boys (age 6.07-19.83 years) as part of the COPENHAGEN Puberty Study. Anthropometry and pubertal stages (PH1-6 and G1-5) were evaluated, and the presence of gynaecomastia was assessed. Non-fasting blood samples were analysed for serum testosterone and morning urine samples were analysed for the total content of 12 phthalate metabolites (MEP, MnBP, MiBP, MBzP, MEHP, MEHHP, MEOHP, MECPP, MiNP, MHiNP, MiONP and MCiOP) by LC-MS/MS. A statistically significant negative correlation was observed between chronological age and the urinary concentration of the sum of measured metabolites DEHP (∑DEHPm) (r = -0.164) and DiNP (∑DiNPm) (r = -0.224), respectively, and the sum of monobutyl phthalate (MBP) isomers (∑MBP((i+n))) (r = -0.139) (all with p < 0.01). In contrast urinary monoethyl phthalate concentration was positively correlated to age (r = 0.187, p < 0.01). The urinary levels of phthalate metabolites were not associated with age at pubertal onset, serum testosterone levels or presence of gynaecomastia. In conclusion, we did not find evidence of anti-androgenic effects of phthalates in our healthy boys. Thus, current phthalate exposure was not associated with pubertal timing, testosterone levels or with the presence of pubertal gynaecomastia in this cross-sectional study. However, longitudinal studies are needed to evaluate possible perinatal or long-term postnatal effects of phthalates on healthy boys.     

Successful gonadotrophin treatment of hypogonadism in postoperative patients with macroprolactinoma and persistent hyperprolactinaemia

We report on two males with prolactinoma in whom hyperprolactinaemia and hypogonadism persisted for several years postoperatively despite the administration of a dopamine agonist or bromocriptine. In these patients, a GnRH test revealed no response in the levels of serum LH or FSH. An hCG stimulation test provoked no response in the serum levels of testosterone. Case 1, who was 28 years old at the first visit, received parenteral testosterone and appreciable virilization of the genitalia was noted within a few months. When he married and desired to father a child, the treatment was switched to hCG/hMG combined therapy and spermatozoa appeared subsequently in the ejaculate, although their numbers were low. His wife conceived and delivered a healthy baby girl. Case 2 was a single young man who presented with hypogonado-trophic hypogonadism and hyperprolactinaemia. He was started on hCG injections three times per week and the maturation of his genitalia was advanced rapidly. Semen analyses showed sperm concentration and motility to be within the normal range. Post-treatment GnRH test revealed no improvement in gonadotrophin responses for LH or FSH. In both cases, the hCG test repeated after the gonadotrophin treatment showed normal basal and stimulated testosterone levels. During the course of gonadotrophin treatment in these cases, serum prolactin levels remained elevated, and it is suggested that, in the two cases, the hypothalamo-pituitary function was disturbed by the tumour or its manipulation and the capacity of the pituitary gland to secrete gonadotrophin was impaired. Under such circumstances with persisting hyperprolactinaemia, hCG and/or hCG/hMG combination treatment can induce normal virilization and advance spermatogenesis sufficiently to achieve fertility.     

Effects of local heating of the testes on the concentration of testosterone in jugular and testicular venous blood of rats and on testosterone production in vitro

Heating both testes of rats to between 39 degrees C and 41 degrees C for 30 min was apparently without effect 21 days later, but heating to between 41.5 degrees C and 43 degrees C for 30 min resulted in a significant drop in testis weight accompanied by significant rises in the serum levels of LH and FSH. There were no changes in serum testosterone concentration in the peripheral circulation although there were increases in the concentration in testicular venous blood. The ability of the heated testis to secrete testosterone in vivo in response to maximal stimulation by hCG was reduced, as judged by testosterone levels in peripheral blood, while there was a supranormal increase in testosterone levels in testicular venous blood. Maximally stimulated testosterone production in vitro by the heated testis was supranormal whereas the basal production of testosterone per testis was not different from control values. Therefore, it appears that the testosterone produced by Leydig cells from heated testes may not be secreted as effectively as in normal testes.