Increased free testosterone but normal 5 alpha-reduced testosterone metabolites in obese premenopausal women.

OBJECTIVE: The aim of the study was to investigate whether the absence of increased 5 alpha-reductase activity explained the absence of hirsutism in premenopausal obese women with increased free testosterone (FT) levels. DESIGN: As in hyperandrogenicity there generally exists evidence for increased 5 alpha-reductase activity, we measured, as parameters of 5 alpha-reductase activity, plasma levels of 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (ADG) and androsterone glucuronide (ADTG) as well as their precursor levels in obese women without hirsutism, obese hirsute women, non-obese hirsute women, and non-obese, non-hirsute women. PATIENTS: Eighty-two premenopausal women (20-45 years old) were studied, in four age matched groups: 39 controls, 18 obese without hirsutism, 11 non-obese hirsute and 14 obese hirsute women. MEASUREMENTS: Blood samples were taken between days 5 and 7 of the menstrual cycle. Steroid hormone levels were measured by radioimmunoassay. Free testosterone levels were measured by equilibrium dialysis. RESULTS: Compared to controls, mean free testosterone levels were increased (P less than 0.01) in obese, obese hirsute and hirsute patients, whereas mean DHEAS levels were increased in hirsute and obese hirsute (P less than 0.01), but not in obese, women. Mean androstanediol glucuronide levels were markedly increased in hirsute and obese hirsute patients (P less than 0.01), but not in obese women. Plasma androsterone glucuronide levels were increased in hirsute (P less than 0.01), in the normal range in obese hirsute, and decreased in obese women (P less than 0.01). CONCLUSIONS: These results show that, despite the presence of higher free testosterone levels, neither 5 alpha-reductase activity (as suggested by normal androstanediol glucuronide levels) nor adrenal androgen precursor levels (DHEAS) are increased in obese women without hirsutism.

Exploration of the testis in infertile men. Relationships among serum levels of FSH, LH, 17-alpha-OH-progesterone and testosterone.

A considerable body of evidence is available indicating a paracrine relationship between the seminiferous tubules and the Leydig cells. In 113 adult subjects in basal conditions the blood levels were determined of FSH (follicle stimulating hormone), LH (luteinizing hormone), 17-alpha-OH-P (17-alpha-OH-progesterone) and T (testosterone) either as a whole or as a free fraction. According to the sperm counts and the FSH levels, the studied subjects were divided into three groups: a group N (Normozoospermia) with sperm counts greater than 20 million/ml and FSH levels of 2.5 +/- 1.5 (mean +/- SD, mIU/ml), a group MO (moderate oligozoospermia) with mild degree of oligozoospermia (5-10 mill) and FSH levels in the range found in group N, a group SO (severe oligozoospermia) with severe degree of oligozoospermia (sperm count less than 5 mill/ml) and FSH levels greater than 2 SD the mean value in the N. Serum levels of LH, 17-alpha-OHP, total T, free T and FSH/LH, LH/T, 17-alpha-OHP/T ratios in group MO and SO were compared with those found in the group N.(ABSTRACT TRUNCATED AT 250 WORDS)

17-a-OH-progesterone to testosterone plasma ratios and their modification after HCG in normal men and in patients with idiopathic infertility.

We have investigated on eventual relationships existing in men between plasma levels of 17-a-OH-Progesterone (17-a-OH-P) and, plasma levels of Testosterone (T) and on the modifications of these relationships after stimulation of the testicles by HCG (Human Chorionic Gonadotropin). An inverse correlation exists between basal plasma levels of the two steroids and their delta max (%max increase 96 h after the injection of 5000 I.U. of hCG): r = -06, p 0.01. This suggests that the enzymatic steps of the delta -4 steroidogenic pathway are rate-limiting for the synthesis of T. The delta max of the two-steroids are also inversely correlated with the circulating levels of LH (Luteinizing Hormone) (r = -05, -06; p less than 0.01) suggesting that the rate-limiting activity of the delta 4 pathway is under endogenous LH control. A desensitized state of this pathway can be expected in presence of high circulating levels of LH. Similarly to LH also the FSH plasma levels, an index of function of the seminiferous tubules, are inversely correlated with the 17-a-OH-P and T delta max (r = -0.4, -05; p 0.005) indicating close relationships between tubular and interstitial functions. In men with idiopathic oligozoospermia and high circulating levels of FSH we have found increased 17-a-OH-P/T ratios after hCG.

Circannual rhythms in reproductive functions of human males, correlations among hormones and hormone-dependent parameters.

In a longitudinal study one healthy man aged 26 yrs underwent semen collections and blood samplings at monthly interval from January to December 1985. The ejaculated samples were analyzed for sperm density, motility, relative proportion of early (ab) and late (cd) spermatids, concentrations of Fructose, L-Carnitine and Transferrin. In a transverse study, 248 serially independent samplings were performed of normal men, 28.9 +/- 7.5 yrs old, consulting for infertility from January 1981 to December 1983. The Cosinor method was employed for searching on circannual rhythms of the studied parameters. The longitudinal study did not detect circannual rhythms of the considered seminal parameters nor of the studied hormones. However, peaks, significantly above the mean values throughout the year (p less than 0.005), were observed of Cortisol, PRL, FSH, LH, Testosterone, Fructose and L-Carnitine levels. Young spermatids and sperm motility showed significant (p less than 0.001) acrophases between June and July; an acrophase was also evident for late spermatids but shifted by six months, between December and January. Mesors and amplitudes were respectively: 28 +/- 1.5 and 9.6 +/- 4.3 (mean +/- SE) for motility; 33.4 +/- 1.6 and 9.9 +/- 5 for early spermatids; 46.6 +/- 1.9 and 13 +/- 6.2 for late spermatids.

Free l-carnitine in human semen.

Spectrophotometrical (412 nm) readings of known amounts of 1-carnitine gave absorbancy changes with minimal interassay variations (8%) in the range of 15.6-125 microM. A 100-microliters volume of seminal plasma was needed for optimal assay repeatability; recoveries of added carnitine were linear (r = 0.998), indicating a sensitivity limit of 0.70 microgram/ml. Intraassay and interassay repeatability gave variation coefficients of 2% and 1.2%, respectively. By this method, 20 samples in duplicate were analyzed within 2 h. Carnitine levels and semen volumes were inversely correlated (r = 0.49). The ejaculated amounts of carnitine (microgram/ejaculate) were not significantly different in 16 normozoospermic subjects and in 13 oligozoospermic patients. Undetectable levels of carnitine were found in case of deferential-vesicular agenesis, and very low levels were found in cases of monorchidism, confirming the epididymides as major producing organs of the substance. Very low levels were also found in semen of men with varicocele, suggesting that seminal carnitine would be regarded as an index of androgenization.

Recovery of fertility in a hypogonadotropic man apparently resistant to gonadotrophin treatment.

Two subjects affected by panhypopituitarism, 17 and 19 years of age, were evaluated. One of the patients was able to ejaculate sperm (14 X 10(6)/ml) after 12 months of hMG-hCG therapy (75 IU 2 degrees IRP HMG + 850 IU hCG twice a week). In the other subject sperm production was not achieved until 6 1/2 years of uninterrupted therapy had been completed although the hCG doses were doubled and then quadrupled. In the patient who responded promptly to the therapy, blood levels of both FSH (2.5) and LH (1.7 (mUI/ml 2 degrees IRP hMG-RIA methods) were indeed detectable through very low. In the patient resistant to the therapy, FSH levels were still detectable (2.2 mUI/ml), but LH was undetectable at all. The seminiferous tubules of this patient contained few spermatogonia, and these would be attributed to the action of FSH by itself. However, the importance of endogenous LH in determining the maturation of the testes is stressed by the very long period of hCG therapy required to obtain in this patient ejaculations of sperm. Careful evaluation must be made of circulating FSH and LH levels, of FSH and LH pituitary stores, and of testicular biopsy scores when assessing prognosis of fertility and adequate treatment of hypogonadotropic subjects. In cases of severe LH deficiency a delayed response of the testis would be expected and recovery of fertility considered possible even when gonadotropin therapy is unsuccessful for many years.

[Sleep and the circadian rhythm of cortisol in transsexuals]. / Sonno e ritmo circadiano del cortisolo in transessuali.

Polygraphic recordings of nocturnal sleep and hormonal behavior were studied in three male and two female transexual subjects, aged 17 to 26 years, who had required a surgical sex reassignment. The transexual state was assayed by psychological investigations according to the law. All subjects appeared healthy at physical examination and no abnormalities were revealed by basal laboratory data. Chromosomal picture was in accordance with sexual characteristics. Pituitary sella enlargements were excluded by radiographic examination. In each patient two adjustment days were followed by polygraphic recording (EEG,EOG,EMG of chin muscles) of nocturnal sleep and blood drawing for cortisol assay. Blood samples were drawn at 30 minutes intervals for 24 hours, starting from the bedding-time. Hormonal blood concentration were determined by radioimmunoassay. Cosinor method was employed in the analysis of circadian rhythm. In transexual subjects the percentage of sleep intermediate phase, or ambiguous sleep, with reference to total sleep time, was significantly higher than in matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)

A degradation product of circulating luteinizing hormone (beta-hCG subunit) in human semen.

Levels of beta-human chorionic gonadotropin (beta-hCG) were detected in semen under basal conditions. No significant correlation to levels of luteinizing hormone (LH) in blood was found. The beta-hCG level did not increase within 3-7 days after a 5000 IU dose of hCG was injected intramuscularly. Human chorionic gonadotropin was detected in semen only after injection. beta-Human chorionic gonadotropin in the semen represents a degradation product of circulating LH.

FSH and LH in human semen: a diagnostic trial for male infertility.

Follicle stimulating hormone (FSH) levels in semen are lower than in blood without any correlation to sperm counts while seminal luteinizing hormone (LH) levels are higher than in blood though with minor values in oligozoospermia and azoospermia conditions. In addition, the FSH levels in semen appear well correlated to those in blood; this type of correlation emerges for LH only in azoospermic patients. The mechanisms which facilitate LH to enter into the semen could be uneffective when spermatogenesis is impaired. If so, undetectable levels of both FSH and LH in semen would indicate obstructive forms of azoospermia while increased levels of LH would indicate the return of a hormonal spermatogenic process in patients undergoing treatment for infertility conditions.

Hormones in the seminal fluid. The transport proteins of the thyroid hormones.

The study of the retention of titrated T3 on columns of Sephadex G-25, (Resin T3 Uptake), in the presence of untreated plasma, or plasma treated with charcoal, indicates that there are very small quantities of protein-hormone compounds present in the seminal fluid. In cases of phlogosis of the genital tract, the increase of albumin in the seminal fluid might determine an increase in the binding capacity with titrated T3. This would therefore give the possibility of a further test in the diagnostics of male infertility.

Hormones in the seminal plasma. Cortisol.

The data from previous studies on the seminal concentrations of proteic hormones result in the hypothesis that there exists a selective filter for these hormones, which is between the systemic circulation and the male genital canal. Previous data regarding sexual steroids are insufficient to verify if such a filter system also operates in the case of hormones of minor molecular weight. It would appear that the study of cortisol, a non-sexual steroid, will be more useful. The concentrations of this hormone in the peripheric blood (176 +/- 59, mean +/- ds, ng/ml) prove to be much greater than in the seminal plasma (20 +/- 9.6). No significant differences are found between normozoospermic and oligo-azoospermic subjects, either in the blood (173 +/- 184 +/- 53), or in the seminal plasma (21 +/- 12 versus 20 +/- 8). These data would seem to support the hypothesis under discussion.

Male fertility and thyroid hormones.

On the basis of the results in vitro, it seems that the testicle does not respond to the action of the thyroid hormones. The study of the relationship between the blood concentrations of these hormones and the reproductive function of the organ is being made by the Authors as a means of verifying this in vivo. The total blood concentrations of T4, (triioothyronine), and the index of free Thyroxine (IT4L) were therefore evaluated both in normal and infertile subjects. The concentrations of T4 showed a correlation both with the sperm count (r = 0.43, p = less than 0.02), and with the percentage of motile spermatozoa, (r = 0.48, p = less than 0.01). This type of correlation is not found, however, either for the T3 or for the IT4L. These data indicate that the function of the thyroid gland is linked to that of the hypothalamo-hypophyseotesticular axis. It would appear that the peripheric metabolism of the circulating hormones is not involved.