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Testosterone concentrations in women aged 25-50 years: associations with lifestyle, body composition, and ovarian status.

While there is substantial evidence of the importance of endogenous and exogenous estrogen in reproductive health and chronic disease, there is little consideration of androgens in women's health. In the Michigan Bone Health Study (1992-1995), the authors examined the correlates of testosterone concentrations in pre- and perimenopausal women (i.e., age, menopausal status, body composition, and lifestyle behaviors) in a population-based longitudinal study including three annual examinations among 611 women aged 25-50 years identified through a census in a midwestern community. Current smokers had the highest testosterone concentrations with decreasing values in former and nonsmokers (p = 0.0001). Body composition measures (body mass index, body fat (%), weight (kg), lean body mass (kg), and fat mass (kg)) were significantly and positively associated with total testosterone concentrations in a dose-response manner. Hysterectomy with oophorectomy was associated with significantly lower testosterone concentrations. Alcohol consumption, physical activity, and dietary macronutrient intake were not associated with testosterone concentrations. This is one of the first studies to examine correlates of serum testosterone concentrations in anticipation of the growing interest in the role of androgens in women's health. The greater circulating levels of testosterone in obese women and smokers suggest that testosterone concentrations should be considered in the natural history of disease conditions where obesity and smoking are risk factors, including cardiovascular disease.

Adult↗

Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status.

BACKGROUND: Loss of muscle mass (sarcopenia) leads to frailty in older men. The decline in testosterone over the life span may contribute to this muscle loss. We studied the ability of oral testosterone to prevent muscle loss in older men over a 12-month period. METHODS: A standard dose (80 mg twice daily) of testosterone undecanoate or placebo was administered for 1 year to 76 healthy men aged 60 years or older. All men had a free testosterone index of 0.3-0.5, which represents a value below the normal lower limit for young men (19-30 years), but remains within the overall normal male range. Measurements of body composition, muscle strength, hormones, and safety parameters were obtained at 0, 6, and 12 months. RESULTS: Lean body mass increased (p =.0001) and fat mass decreased (p =.02) in the testosterone as compared with the placebo-treated group. There were no significant effects on muscle strength. There was a significant increase in hematocrit (0.02%) in the testosterone-treated group (p =.03). Plasma triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels were similar in both groups, but there was a decrease in high-density lipoprotein cholesterol (-0.1 mmol/L) at 12 months in the testosterone group as compared to the placebo group (p = 0.026). There were no differences in prostate-specific antigen or systolic or diastolic blood pressure between the groups. CONCLUSION: Oral testosterone administration to older relatively hypogonadal men results in an increase in muscle mass and a decrease in body fat.

Adipose Tissue↗

Serum testosterone and testicular response to HCG in young and aged male rats.

Serum testosterone and testicular response to HCG was measured in young (3 - 6 mo) and aged (20 - 30 mo) male Long-Evans rats. Serum testosterone was measured by radioimmunoassays on serial blood samples taken before and after injections of HCG. Control group serum testosterone concentrations were lower in aged compared to young groups. Intravenous injection of 1, 5, and 20 IU of HCG increased serum testosterone in both age groups and testosterone remained elevated throughout the 150-min sampling interval. The increase in serum testosterone concentrations following acute HCG stimulation was greater in young than in aged rats. Serum testosterone concentrations and testicular response to intravenous HCG injections were increased to similar levels in young and aged male rats following 7 days of daily subcutaneous injections of 5 IU of HCG/100 gm bw. These data suggest that while testicular secretion and responsiveness is reduced with age, the aged male rat retains the capacity to secrete more testosterone than it normally maintains.

Aging↗

The epidemiology of plasma testosterone levels in middle-aged men.

Several diseases, e.g., coronary heart disease, cancer, etc., have been related to sex hormones. Thus, research on the epidemiology of sex hormones may be productive. The epidemiologic study of testosterone has been limited due to the circadian and circannual variations and the wide interindividual variability. The authors evaluated the reliability and repeatability of a single blood draw to measure individual plasma testosterone levels in three pilot studies. The results indicated that the measurements of the hormone level are highly repeatable and a single morning specimen appeared to be sufficient for characterization of individual testosterone levels. Research then focussed on 243 men in the Multiple Risk Factor Intervention Trial to investigate the determinants of plasma testosterone level. The results indicated that age and obesity were significantly correlated with plasma testosterone level. (The multiple R of these two variables in the multiple regression analysis for plasma total testosterone was 0.32.) Smoking was positively related to testosterone through a relationship with age. Daily physical activity, history of alcohol intake, and behavior factors of A and B behavior types were not found to be related to testosterone concentrations.

Adult↗

Evaluation of the 20-day pubertal female assay in Sprague-Dawley rats treated with DES, tamoxifen, testosterone, and flutamide.

The Endocrine Disrupter Screening and Testing Advisory Committee (EDSTAC) has recommended the rodent pubertal female assay as a Tier I test to detect potential endocrine disrupters (EDs). This assay is designed to screen estrogenic activity in immature rats exposed to chemicals during sexual maturation. The aim of this study was to evaluate whether this assay can detect the EDs with effects brought about through various mechanisms. Immature Sprague-Dawley female rats (21 days of age) were dosed daily for 20 days by oral gavage (DES, tamoxifen, and flutamide) or sc injection (testosterone). The mean age at vaginal opening (VO) was 32.3 +/- 0.5 days in control rats. Although VO was unaffected by DES at doses of 0.2 and 1.0 microg/kg, a high dose of DES (5.0 microg/kg) significantly advanced the age at VO to 24 days. Both tamoxifen (50 and 200 microg/kg) and flutamide (25 mg/kg) also significantly accelerated VO to 27.8 +/- 0.5, 25.1 +/- 0.1, and 26.1 +/- 0.1, respectively. However, testosterone dose-dependently delayed VO (exposure to 1.0 mg/kg extended VO to 37.3 +/- 0.8 days, and VO did not occur in 2 of 10 animals by the time of necropsy at 41 days of age). Estrous cyclicity was monitored in rats from VO to necropsy. Irregular cycles were observed in the groups treated with DES (5.0 microg/kg), tamoxifen (200 microg/kg), testosterone (1.0 mg/kg), and flutamide (25 mg/kg). High dose of DES showed a persistent estrus state throughout the entire observation period. In addition, the number of days in diestrus was increased by tamoxifen (200 microg/kg) and flutamide (25 mg/kg) treatments. Significant decreases in ovarian weight were observed in 5.0 microg/kg DES (64% of control), 25 mg/kg flutamide (76% of control), and 200 microg/kg tamoxifen (47% of control). Testosterone also significantly decreased the ovarian weights in all treatment groups. Uterine weights were also decreased significantly at high doses of tamoxifen (200 microg/kg, 39% of control) or testosterone (1.0 mg/kg, 47% of control). In hormone analysis, tamoxifen significantly increased serum E(2) levels at 50 microg/kg. The mean serum levels of TSH were significantly increased in tamoxifen (10 and 50 microg/kg), testosterone (0.2 mg/kg), and flutamide (1.0 and 25 mg/kg) treatment groups compared with the control. However, serum T(4) levels were significantly reduced by testosterone. Furthermore, serum T(3) levels were significantly increased in DES, tamoxifen (10 and 50 microg/kg), testosterone (1.0 mg/kg), and flutamide (1.0 and 5 mg/kg). Our data demonstrate that the rodent pubertal female assay is useful for identifying potential EDs having not only estrogenic/antiestrogenic but also androgenic/antiandrogenic activities. However, further validation study is necessary to identify chemicals that operate through other action mechanisms, including steroid biosynthesis inhibitors and thyroid inhibitors. Moreover, additional data on other compounds with weak endocrine disrupting activity will be required to further characterize the sensitivity of the female pubertal assay.

Administration, Oral↗

Insulin augmentation of testosterone production in a primary culture of rat testicular cells.

The direct effects of insulin on basal and human chorionic gonadotropin (hCG)-stimulated accumulation of testosterone were investigated in vitro using a primary culture system of rat testicular cells from adult hypophysectomized male rats. The basal accumulation of testosterone was low throughout the 10-day incubation period. Treatment of testicular cells with insulin (10 micrograms/ml) by itself was without effect on the basal accumulation of testosterone, while treatment with increasing concentrations (0.1--10 ng/ml) of hCG resulted in dose-dependent increases in the accumulation of testosterone. Furthermore, concomitant treatment with increasing concentrations (0.01--10 micrograms/ml) of insulin led to a dose-dependent augmentation (up to 116% on Day 10) in the hCG-stimulated accumulation of testosterone, as well as a 1.6-fold increase in the testicular responsiveness to hCG. In contrast, treatment with desoctapeptide insulin (10 micrograms/ml), a trypsin degraded insulin, was without effect on the hCG-stimulated accumulation of testosterone. Increasing duration (12--72 h) of treatment with insulin resulted in time-dependent increases in the hCG-stimulated accumulation of testosterone achieving statistical significance (P less than 0.05) by 36 h. In addition, pretreatment with insulin (10 micrograms/ml) brought about significant (P less than 0.01) increases in the choleragen and Bt2cAMP-stimulated accumulation of testosterone. The augmenting effect of insulin was equally effective upon culturing in a glucose-free medium and was not associated with significant alterations in testicular cell number or cellular DNA or protein content. It is concluded that diminished testicular steroidogenesis in the diabetic rats may represent, at least in part, a direct consequence of insulin deficiency at the testicular level and that insulin may play an important role in the augmentation of testicular androgen production.

Animals↗

Effects of active immunization against estradiol-17 beta on luteinizing hormone and testosterone in male rats.

The role of endogenous estradiol-17 beta (E2) in regulating luteinizing hormone (LH) and testosterone secretion was investigated in adult male rats actively immunized against the E2-bovine serum albumin (BSA) conjugate. The antigen was injected intradermally 4 times at 2-week intervals and additional boosters were continued once a month. A pooled antiserum from immunized animals cross-reacted 8% to estrone, 1% to testosterone and 5 alpha-dihydrotestosterone, and less than 1% to estradiol-17 alpha, estriol, dehydroepiandrosterone, corticosterone, cortisol, progesterone and 20 alpha-dihydroprogesterone when compared with E2 (100%). Serum E2 in immunized rats was not adsorbed with dextran-coated charcoal, indicating that most of the serum E2 was bound to the antibody. In serum of immunized rats, LH and testosterone concentrations were significantly higher than those in intact rats. The metabolic clearance rate of testosterone was not changed, but the production rate of testosterone was significantly increased by the immunization. By the implantation of a micropellet of E2 in one testis, testosterone concentrations in the testicular vein blood from either the implanted or intact side were significantly decreased in intact rats, but not in immunized rats. In both groups, there were no significant differences between the testosterone concentration in testicular vein blood in the implanted and intact sides. It is concluded that circulating E2 physiologically participates in maintaining LH-testosterone homeostasis by inhibiting LH secretion in adult male rats.

Animals↗

Effects of gonadotropin-releasing hormone pulse-frequency modulation on luteinizing hormone, follicle-stimulating hormone and testosterone secretion in hypothalamo/pituitary-disconnected rams.

The effects of changes in pulse frequency of exogenously infused gonadotropin-releasing hormone (GnRH) were investigated in 6 adult surgically hypothalamo/pituitary-disconnected (HPD) gonadal-intact rams. Ten-minute sampling in 16 normal animals prior to HPD showed endogenous luteinizing hormone (LH) pulses occurring every 2.3 h with a mean pulse amplitude of 1.11 +/- 0.06 (SEM) ng/ml. Mean testosterone and follicle-stimulating hormone (FSH) concentrations were 3.0 +/- 0.14 ng/ml and 0.85 +/- 0.10 ng/ml, respectively. Before HPD, increasing single doses of GnRH (50-500 ng) elicited a dose-dependent rise of LH, 50 ng producing a response of similar amplitude to those of spontaneous LH pulses. The effects of varying the pulse frequency of a 100-ng GnRH dose weekly was investigated in 6 HPD animals; the pulse intervals explored were those at 1, 2, and 4 h. The pulsatile GnRH treatment was commenced 2-6 days after HPD when plasma testosterone concentrations were in the castrate range (less than 0.5 ng/ml) in all animals. Pulsatile LH and testosterone secretion was reestablished in all animals in the first 7 days by 2-h GnRH pulses, but the maximal pulse amplitudes of both hormones were only 50 and 62%, respectively, of endogenous pulses in the pre-HPD state. The plasma FSH pattern was nonpulsatile and FSH concentrations gradually increased in the first 7 days, although not to the pre-HPD range. Increasing GnRH pulse frequency from 2- to 1-hour immediately increased the LH baseline and pulse amplitude. As testosterone concentrations increased, the LH responses declined in a reciprocal fashion between Days 2 and 7. FSH concentration decreased gradually over the 7 days at the 1-h pulse frequency. Slowing the GnRH pulse to a 4-h frequency produced a progressive fall in testosterone concentrations, even though LH baselines were unchanged and LH pulse amplitudes increased transiently. FSH concentrations were unaltered during the 4-h regime. These results show that 1) the pulsatile pattern of LH and testosterone secretion in HPD rams can be reestablished by exogenous GnRH, 2) the magnitude of LH, FSH, and testosterone secretion were not fully restored to pre-HPD levels by the GnRH dose of 100 ng per pulse, and 3) changes in GnRH pulse frequency alone can influence both gonadotropin and testosterone secretion in the HPD model.

Animals↗

Development and validation of a fecal testosterone biomarker in Mus musculus and Peromyscus maniculatus.

This is a report on the development and validation of an ELISA method to determine fecal testosterone levels, and on their evaluation as a biomarker for adverse effects of endocrine-disrupting chemicals on reproductive health using male rodents of the Peromyscus maniculatus and Mus musculus species as an animal model. The ELISA antibody had the highest specificity for testosterone (100%), followed by dihydrotestosterone (57.4%) and androstenediol (0.27%). Radiolabeled testosterone was injected i.p. into three mice. Fecal samples were collected, extracted, and analyzed by liquid scintillation counting. The ELISA was performed to characterize the excretion kinetics and metabolic fate of circulating testosterone. Solubilization of feces with 10% methanol overnight provided an extraction efficiency of 87% for all metabolites; an ethyl ether extraction was more selective for testosterone. The fecal excretion of the testosterone was a biphasic process with a majority of the radioactivity recovered in the first 24 hours. HPLC analysis revealed at least five testosterone metabolites in feces, with most metabolites being less polar than testosterone. This study forms the initial evaluation of what will become a field monitoring tool.

Androstenediol↗

Testosterone inhibits 11-ketotestosterone-induced spermatogenesis in African catfish (Clarias gariepinus).

Male fish produce 11-ketotestosterone as a potent androgen in addition to testosterone. Previous experiments with juvenile African catfish (Clarias gariepinus) showed that 11-ketotestosterone, but not testosterone, stimulated spermatogenesis, whereas testosterone, but not 11-ketotestosterone, accelerated pituitary gonadotroph development. Here, we investigated the effects of combined treatment with these two types of androgens on pituitary gonadotroph and testis development. Immature fish were implanted for 2 wk with silastic pellets containing 11-ketotestosterone, testosterone, 5alpha-dihydrotestosterone, or estradiol-17beta; cotreatment groups received 11-ketotestosterone in combination with one of the other steroids. Testicular weight and pituitary LH content were higher (two- and fivefold, respectively) in the end control than in the start control group, reflecting the beginning of normal pubertal development. Treatment with testosterone or estradiol-17beta further increased the pituitary LH content four- to sixfold above the end control levels. This stimulatory effect on the pituitary LH content was not modulated by cotreatment with 11-ketotestosterone. However, the stimulatory effect of 11-ketotestosterone on testis growth and spermatogenesis was abolished by cotreatment with testosterone, but not by cotreatment with estradiol-17beta or 5alpha-dihydrotestosterone. Also, normal pubertal testis development was inhibited by prolonged (4 wk) treatment with testosterone. The inhibitory effect of testosterone may involve feedback effects on pituitary FSH and/or on FSH receptors in the testis. It appears that the balanced production of two types of androgens, and the control of their biological activities, are critical to the regulation of pubertal development in male African catfish.

Animals↗

Temporal effects of testosterone propionate injections on serum lipoprotein concentrations in rats.

UNLABELLED: The chronic abuse of androgenic anabolic steroids, a group of synthetic derivatives of testosterone, to improve athletic performance have demonstrated compromised serum lipoprotein concentrations reflecting an elevated risk for cardiovascular disease. While the detrimental alterations in the lipoprotein profile have been reported consistently for orally administered androgenic anabolic steroids, the reports examining the effects of parenteral administration of testosterone upon the lipid profile remain equivocal. PURPOSE: The purpose of this study was to determine whether compromised serum lipoprotein concentrations would be manifest in rats receiving testosterone injections (twice per week) over the time course of 7 wk. METHODS: Male rats were randomly assigned to either an experimental group (dose per injection, 3 mg x kg(-1) testosterone propionate solubilized in 1 mL of safflower oil) or a control group (injected with an isovolumic amount of safflower oil alone). The effects of the steroid regimen on the serum lipoprotein profiles were followed after 1, 3, 5, and 7 wk of injections. To assess the relative effects of testosterone propionate, testicular mass was determined at the time of sacrifice. RESULTS: Testicular mass (mean +/- SE) was significantly lower (P<0.01) in the experimental group, 3.08+/-0.03 g, compared with that in controls, 3.82+/-0.05 g, by week 3 and continued to decline for the remainder of the steroid regimen, reaching a nadir of 2.70+/-0.01 g at week 5. No significant differences were observed between groups for total serum cholesterol, serum triacylglycerols, or serum low density lipoprotein (LDL)-C at any time point. However, at week 7, serum high density lipoprotein (HDL)-C (mean +/- SE) was significantly lower (P<0.02) in the testosterone treated animals, 32+/-2 mg x dL(-1), compared with that in controls, 47+/-2 mg x dL(-1). As a result, the ratio of total cholesterol to HDL-C (mean +/- SE) significantly increased (P<0.02) by the seventh week in the testosterone treated group, 3.5+/-0.2, versus controls, 2.5+/-0.2. CONCLUSIONS: The results suggest that while testosterone propionate injections elicit a reduction in testicular mass within 3 wk, the lipoprotein profile is not altered until week 7. Further, the only compromised parameter under the conditions of this study is the decrease in serum HDL-C.

Analysis of Variance↗

Oestradiol and testosterone blood levels in patients with viral cirrhosis and hepatocellular carcinoma.

BACKGROUND: Patients with alcoholic cirrhosis show hypogonadism and feminization associated with sex hormone imbalance due to enhanced aromatization of testosterone and subsequent reduced testosterone and increased oestradiol blood levels. Because oestrogens modulate hepatocyte proliferation and oestrogen receptors are present in liver cirrhosis and hepatocellular carcinoma, it has been proposed that sex hormone imbalance can play a role in liver carcinogenesis. Trials with the oestrogen receptor antagonist tamoxifen have been performed with conflicting results. OBJECTIVES: To investigate oestradiol and testosterone blood levels in men with viral cirrhosis and hepatocellular carcinoma and also to investigate changes in sex hormone circulating levels induced by tamoxifen treatment. PATIENTS AND METHODS: Oestradiol and testosterone blood levels were evaluated in 32 male patients with postviral cirrhosis and hepatocellular carcinoma at the time of diagnosis and during the follow-up, and in 20 healthy controls. In eight patients, hormone levels were also assayed during treatment with tamoxifen (40 mg/day). No patient had a history of high alcohol intake. RESULTS: Oestradiol values observed at the time of diagnosis were 56.1 +/- 54.5 pmol/l, while testosterone values were 13.6 +/- 8.0 pmol/l. There was no relationship between oestrogen values and age, while higher oestradiol values were observed in patients with advanced cirrhosis (Child B and C); conversely, testosterone levels progressively and significantly decreased from cirrhosis Child A (15.1 +/- 9.7) to C (7.7 +/- 7.1) (P < 0.05). Tamoxifen treatment (40mg/day) for 1 month in eight patients increased oestradiol values (62.2 +/- 77.0 vs. 156.4 +/- 83 pmol/l, P < 0.05), while testosterone levels decreased (15.1 +/- 6.8 vs. 8.5 +/- 10.6 pmol/l). However, these changes were not associated with clinical signs or symptoms of feminization. Oestrogen levels decreased after 6 months of tamoxifen treatment. No significant change in hormone levels was observed in patients not treated with tamoxifen. Unlike patients with alcoholic cirrhosis, in male patients with viral cirrhosis and hepatocellular carcinoma there were no significant alterations in blood oestradiol and testosterone levels, although a certain degree of sex hormone imbalance was observed in those with advanced cirrhosis. Treatment with tamoxifen (40 mg/day) did not induce clinical manifestations of sex hormone imbalance.

Age Factors↗

Testosterone increases perceived dominance but not attractiveness in human males.

Recent evidence suggests that certain features on the human face indicate hormonal levels during growth, and that women judge the attractiveness of potential partners based on the appearance of these features. One entrenched notion is male facial features that are affected by testosterone are used as direct cues in mate preference. Testosterone may be particularly revealing as it is purported to be an honest indicator of male fitness. Increased testosterone may impose an immunocompetence handicap on the bearer and only the best males can carry this handicap. To date, tests of this theory have been indirect, and have relied on digital manipulations that represent unrealistic continuums of masculine and feminine faces. We provide a much more direct test by manipulating digitally male faces to mimic known shape variation, caused by varying levels of testosterone through puberty. We produced a continuum of faces that ranged from low to high levels of testosterone in male faces and asked women to choose the points on the continuum that appeared most attractive and most physically dominant. Our data indicate that high testosterone faces reveal dominance. However, there is no evidence of directional selection for increased (or decreased) testosterone in terms of attractiveness to the opposite sex. We discuss the relevance and applicability of evolutionary interpretations of our data and, contrary to predictions, provide evidence of stabilizing selection acting on testosterone through mate preferences.

Adolescent↗

Competition for male reproductive investment elevates testosterone levels in female dunnocks, Prunella modularis.

In many songbirds, females occasionally sing in contexts of high female-female competition. Testosterone may be involved in the activation of song, because testosterone implants elicit female song in many species with rare female song. A possible mechanism for the hormonal control of female song is provided by the challenge hypothesis, which predicts a rise in testosterone in response to aggressive interactions during socially unstable situations. We tested this by comparing faecal testosterone levels in polygynandrous and monogamous female dunnocks. In groups with two to three females (polygynandry and polygyny) males provide less help at each nest than in groups with a single female (monogamy and polyandry). Polygynandrous and polygynous females are aggressive towards one another and attempt to expel rivals. Polygynandrous females had significantly higher testosterone levels than monogamous females. Competition between females that was induced by removal of males caused testosterone levels to rise. Further, female testosterone levels were correlated with the rate of 'tseep' calls, which are produced during aggressive encounters between females. Finally, polygynandrous and polygynous females sang significantly more than monogamous females. To the best of our knowledge, these results provide the first experimental support for the challenge hypothesis in female birds, and suggest that testosterone can regulate facultative female song in songbirds.

Animals↗

Chronic treatment regimens for hirsutism in women: effect on blood production rates of testosterone and on hair growth.

Twenty-five women with hirsutism were studied before and during treatment aimed empirically at suppresing testosterone production by adrenals, ovaries or both. Mean basal plasma testosterone was 70 plus or minus 30 ng/dl, significantly (P less than 0.01) higher than the mean of twenty-three normal women; basal metabolic clearance rate (MCR) of testosterone was also higher (P less than 0.01) than that reported for normal women. Production rate (PR) of testosterone exceeded 417 mug/24 h (1 SD above the mean reported for normal women), in nineteen of the twenty-five patients. After 4 months, small dose betamethasone therapy (0.5 mg at bed time) had reduced the mean PR of testosterone in thirteen patients from 509 mug/24 h to 356 mug/24 h (P = 0.05); anovulatory steroids reduced mean PR of testosterone in nine from 612 mug/24 h to 345 mug/24 h (P less than 0.05, greater than 0.025), and the combination of both therapies in ten reduced PR of testosterone from 528 mug/24 h to 148 mug/24 h (P less than 0.001). The latter regimen had moderate success in reducing hair growth (in six out of ten). Fourteen of the twenty-five claimed benefit in hirsutism and all thirteen with acne were improved. In individual cases, clinical benefit did not correlate well with reduction in PR of testosterone. Freedom from undesirable side effects allows these well-accepted forms of treatment to be given even longer trials.

Acne Vulgaris↗

Relationship of changes in serum concentrations of prolactin and testosterone during dopaminergic modulation in males.

To evaluate the effect of PRL on the male pituitary-gonadal system, serum concentrations of PRL, testosterone, LH and FSH were determined in healthy young men daily before, during, and after 3-day oral administration of bromocriptine, metoclopramide or sulpiride. Bromocriptine (2.5 mg as a single dose) caused, concurrently with a marked suppression of serum PRL, a significant increase of serum testosterone and a transient decrease of serum LH. The changes of PRL and testosterone were negatively correlated. With metoclopramide (10 mg q.i.d.) serum PRL was increased and testosterone inversely decreased. There was no change in LH and FSH. Sulpiride (50 mg q.i.d.) evoked the elevation of serum PRL and LH, but no change in testosterone. A significant increase in serum concentration of testosterone was also observed in a patient with PRL-producing pituitary tumour and four out of seven patients with acromegaly during bromocriptine treatment. These results suggest an inhibitory effect of PRL on testosterone secretion at the gonadal level, or direct dopaminergic stimulatory control of testosterone secretion.

Acromegaly↗

Circadian rhythm of plasma testosterone in men with idiopathic hypogonadotrophic hypogonadism before and during pulsatile administration of gonadotrophin-releasing hormone.

OBJECTIVE: The aim was to investigate whether a pulsatile discharge of LH from the pituitary is necessary to achieve the circadian secretion of testosterone. DESIGN: The daily rhythm of the androgen has been studied in patients with idiopathic hypogonadotrophic hypogonadism (IHH) both in the absence of therapy and during pulsatile administration of gonadotrophin releasing hormone (GnRH). PATIENTS: Six patients with IHH and ten normal subjects were analysed. Blood sampling was performed at 2-hourly intervals, for 24 hours. The IHH patients then received synthetic GnRH i.v. at the rate of one pulse every 2 hours (10 micrograms/pulse). On day 11 of treatment, blood samples were taken for the rhythm analysis every 2 hours, for 24 hours. MEASUREMENTS: Plasma testosterone and LH were measured in the individual samples by radioimmunoassay. Evaluation of the rhythm was performed by cosinor analysis. RESULTS: A significant circadian rhythm of plasma testosterone was statistically validated in the normal subjects, whereas no rhythm was detected in the IHH patients in the absence of therapy. On day 11 of GnRH pulsatile administration the IHH patients showed normal testosterone levels and a statistically significant circadian rhythm of the androgen was evident, with acrophase between 0700 and 0800 h. Moreover, the amplitude, acrophase and mesor of testosterone rhythm in IHH patients in the course of treatment were statistically indistinguishable from the corresponding values in the normal subjects. Plasma LH did not show statistically significant circadian variations, either in the control group or in the IHH patients before or during therapy. CONCLUSIONS: We conclude that a physiological circadian rhythm of plasma testosterone can be obtained, in IHH men, by treatment with GnRH. Since the pulsatile administration of exogenous GnRH at constant doses induced a circadian rhythm in testosterone and no daily variations in LH were evident, we suggest that, although a pulsatile secretion of LH is probably necessary for the synchronization of the circadian rhythm with acrophase in the morning, the testosterone variations might be the results of a local testicular modulation of LH action.

Adult↗

Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis.

OBJECTIVES: Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass, accumulation of central adiposity, impaired mobility and increased risk of bone fractures. Whether androgen treatment might be beneficial in these subjects is still under debate. We have carried out a systematic review of randomized controlled trials (RCTs) evaluating the effects of testosterone (T) administration to middle-aged and ageing men on body composition, muscle strength, bone density, markers of bone metabolism and serum lipid profile. DATA SOURCE: A comprehensive search of all published randomized clinical trials was performed using the MEDLINE, Cochrane Library, EMBASE and Current Contents databases. REVIEW METHODS: Guided by prespecified criteria, software-assisted data abstraction and quality assessed by two independent reviewers, 29 RCTs were found to be eligible. For each investigated variable, we reported the results of pooled estimates of testosterone treatment using the random effect model of meta-analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta-regression analysis. RESULTS: Overall, 1,083 subjects were evaluated, 625 randomized to T, 427 to placebo and 31 to observation (control group). Weighted mean age was 64.5 years (range 49.9--77.6) and mean serum testosterone was 10.9 nmol/l (range 7.8--19). Testosterone treatment produced: (i) a reduction of 1.6 kg (CI: 2.5--0.6) of total body fat, corresponding to -6.2% (CI: 9.2--3.3) variation of initial body fat, (ii) an increase in fat free mass of 1.6 kg (CI: 0.6--2.6), corresponding to +2.7% (CI: 1.1--4.4) increase over baseline and (iii) no change in body weight. The effects of T on muscle strength were heterogeneous, showing a tendency towards improvement only at the leg/knee extension and handgrip of the dominant arm (pooled effect size=0.3 standard mean difference (SMD), CI: -0.0 to 0.6). Testosterone improved bone mineral density (BMD) at the lumbar spine by +3.7% (CI: 1.0--6.4%) compared to placebo, but not at the femoral neck, and produced a consistent reduction in bone resorption markers (pooled effect size = -0.6 SMD, CI: -1.0 to -0.2). Testosterone also reduced total cholesterol by 0.23 mmol/l (CI: -0.37 to -0.10), especially in men with lower baseline T concentrations, with no change in low density lipoprotein (LDL)-cholesterol. A significant reduction of high density lipoprotein (HDL)-cholesterol was found only in studies with higher mean T-values at baseline (-0.085 mmol/l, CI: -0.017 to -0.003). Sensitivity and meta-regression analysis revealed that the dose/type of T used, in particular the possibility of aromatization, explained the heterogeneity in findings observed on bone density and HDL-cholesterol among studies. CONCLUSION: The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men. Our findings are sufficiently strong to justify further interventional studies focused on alternative targets of androgenic treatment carrying more stringent clinical implications, in particular the cardiovascular, metabolic and neurological systems.

Adult↗