scholarly journals Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism

2008 ◽  
Vol 158 (5) ◽  
pp. 741-747 ◽  
Author(s):  
Sandra Loves ◽  
Janneke Ruinemans-Koerts ◽  
Hans de Boer

ObjectiveIsolated hypogonadotropic hypogonadism (IHH) is frequently observed in severely obese men, probably as a result of increased estradiol (E2) production and E2-mediated negative feedback on pituitary LH secretion. Aromatase inhibitors can reverse this process. This study evaluates whether letrozole once a week can normalize serum testosterone in severely obese men and maintain its long term effect.DesignOpen, uncontrolled 6-month pilot study in 12 severely obese men (body mass index>35.0 kg/m2) with obesity-related IHH and free testosterone levels <225 pmol/l, treated with 2.5 mg letrozole once a week for 6 months.ResultsSix weeks of treatment reduced total E2 from 123±11 to 58±7 pmol/l (P<0.001, mean±s.e.m.), and increased serum LH from 4.4±0.6 to 11.1±1.5 U/l (P<0.001). Total testosterone rose from 5.9±0.5 to 19.6±1.4 nmol/l (P<0.001), and free testosterone from 163±13 to 604±50 pmol/l (P<0.001). Total testosterone rose to within the normal range in all subjects, whereas free testosterone rose to supraphysiological levels in 7 out of 12 men. The testosterone and E2 levels were stable throughout the week and during the 6-month treatment period.ConclusionLetrozole 2.5 mg once a week produced a sustained normalization of serum total testosterone in obese men with IHH. However, free testosterone frequently rose to supraphysiological levels. Therefore, a starting dose <2.5 mg once a week is recommended.

2018 ◽  
Vol 126 (03) ◽  
pp. 176-181
Author(s):  
Mark Livingston ◽  
Richard Jones ◽  
Geoff Hackett ◽  
Gemma Donnahey ◽  
Gabriela Moreno ◽  
...  

Abstract Background Testosterone, the most important androgen produced by the testes, plays an integral role in male health. Testosterone levels are increasingly being checked in primary healthcare as awareness of the risks of male hypogonadism grows. Aim To investigate what tests are performed to screen for hypogonadism and to exclude secondary hypogonadism. Design and Setting All participants attended general practices in the UK. Methods Data search was performed using the EMIS® clinical database (provider of the majority of GP operating systems in Cheshire). The anonymised records of male patients aged 18–98 years who had undergone a check of serum testosterone during a 10-year period were analysed. Results Overall screening rate was 4.3%. Of 8 788 men with a testosterone result, 1 924 men (21.9%) had a total testosterone level <10 nmol/L. Just 689 of 8 788 men (7.8%) had a sex hormone-binding globulin (SHBG) result, corresponding to 30.5% of those potentially hypogonadal. Estimated free testosterone was negatively associated with BMI (Spearman’s rho -0.2, p<0.001) as was total testosterone in the over 50 s. Of 1 924 potentially hypogonadal men with a serum testosterone <10 nmol/L, 588 of 1 924 (30.6%) had a check of serum prolactin. 46.3% and 41.7% had LH and FSH measured, respectively. Only 19.1% of 1 924 men with a hypogonadal total testosterone level were subsequently put on testosterone replacement. The percentage of men in the relatively socially disadvantaged category was similar for both eugonadal and hypogonadal men with a much higher rate of screening for hypogonadism in more socially advantaged men. Conclusions Screening in primary healthcare identified a significant minority of men who had potential hypogonadism. Interpretation of a low serum testosterone requires measurement of serum prolactin, LH and FSH in order to rule out secondary hypogonadism. We suggest that this becomes part of routine screening with a balanced screening approach across the socioeconomic spectrum.


1984 ◽  
Vol 100 (1) ◽  
pp. 33-41 ◽  
Author(s):  
H. F. S. Huang ◽  
P. Zaidi ◽  
E. Nieschlag

ABSTRACT Pituitary–testicular relationships in mature male rats were investigated during the period of germinal involution after the induction of vitamin A deficiency (VAD). Vitamin A deficiency caused a decrease in testicular weight, a gradual increase in the incidence of delayed spermiation, increased phagocytosis of spermatids and pyknosis of germ cell nuclei in rats aged 80 to 110 days. Both basal and gonadotrophin releasing hormone (GnRH)-stimulated serum FSH concentrations were increased by 100 days of age. During the same period, the per cent increment in GnRH-stimulated FSH secretion, pituitary FSH concentration and LH secretion remained unchanged. These results suggest that the increased serum FSH may mark specifically an alteration in the germinal epithelium. By 140 days of age, spermatogenic activity in the rats with VAD was limited to the spermatogonial proliferations so that only Sertoli cells, spermatogonia and preleptotene spermatocytes remained. At this time hypersecretion of FSH persisted while the per cent increment of GnRH-stimulated FSH secretion decreased. Concomitantly, basal and GnRH-stimulated LH concentrations were also increased in the presence of normal serum testosterone. These results indicate that a complete cessation of spermatogenesis beyond preleptotene spermatocytes is associated with a change in the secretion of both FSH and LH. The relationship between serum LH and testosterone was normal until at least 110 days of age. By 140 days the ratio between basal LH and basal testosterone, and between total LH and total testosterone, after GnRH administration, increased in the rats with VAD. These changes may be caused by a hyporesponsiveness of the Leydig cells which may, in turn, be attributed to the cessation of spermatogenesis. J. Endocr. (1984) 100, 33–41


2020 ◽  
Vol 27 (12) ◽  
pp. 1186-1191
Author(s):  
Giuseppe Grande ◽  
Domenico Milardi ◽  
Silvia Baroni ◽  
Andrea Urbani ◽  
Alfredo Pontecorvi

Male hypogonadism is “a clinical syndrome that results from failure of the testis to produce physiological concentrations of testosterone and/or a normal number of spermatozoa due to pathology at one or more levels of the hypothalamic– pituitary–testicular axis”. The diagnostic protocol of male hypogonadism includes accurate medical history, physical exam, as well as hormone assays and instrumental evaluation. Basal hormonal evaluation of serum testosterone, LH, and FSH is important in the evaluation of diseases of the hypothalamus-pituitary-testis axis. Total testosterone levels < 8 nmol/l profoundly suggest the diagnosis of hypogonadism. An inadequate androgen status is moreover possible if the total testosterone levels are 8-12 nmol/L. In this “grey zone” the diagnosis of hypogonadism is debated and the appropriateness for treating these patients with testosterone should be fostered by symptoms, although often non-specific. Up to now, no markers of androgen tissue action can be used in clinical practice. The identification of markers of androgens action might be useful in supporting diagnosis, Testosterone Replacement Treatment (TRT) and clinical follow-up. The aim of this review is to analyze the main findings of recent studies in the field of discovering putative diagnostic markers of male hypogonadism in seminal plasma by proteomic techniques. The identified proteins might represent a “molecular androtest” useful as a seminal fingerprint of male hypogonadism, for the diagnosis of patients with moderate grades of testosterone reduction and in the follow-up of testosterone replacement treatment.


1993 ◽  
Vol 128 (4) ◽  
pp. 351-354 ◽  
Author(s):  
Lise Duranteau ◽  
Philippe Chanson ◽  
Joelle Blumberg-Tick ◽  
Guy Thomas ◽  
Sylvie Brailly ◽  
...  

We investigated the potential pituitary origin of gonadal insufficiency in hemochromatosis. Gonadotropin secretion was studied in seven patients with hemochromatosis and hypogonadism, before and after chronic pulsatile GnRH therapy. Pulsatile LH secretion was studied before (sampling every 10 min for 6 h) and after 15-30 days of chronic pulsatile GnRH therapy (10-12 μg per pulse). Prior to GnRH therapy, all the patients had low serum testosterone, FSH and LH levels. LH secretion was non-pulsatile in four patients, while a single pulse was detected in the remaining three. Chronic pulsatile GnRH administration did not increase serum testosterone levels; similarly, serum LH levels remained low: neither pulse frequency nor pulse amplitude was modified. We conclude that hypogonadism in hemochromatosis is due to pituitary lesions.


2002 ◽  
Vol 92 (1) ◽  
pp. 142-146 ◽  
Author(s):  
Gregory A. Brown ◽  
Emily R. Martini ◽  
B. Scott Roberts ◽  
Matthew D. Vukovich ◽  
Douglas S. King

The effectiveness of orally ingested androstenediol in raising serum testosterone concentrations may be limited because of hepatic breakdown of the ingested androgens. Because androstenediol administered sublingually with cyclodextrin bypasses first-pass hepatic catabolism, we evaluated the acute hormonal response to sublingual cyclodextrin androstenediol supplement in young men. Eight men (22.9 ± 1.2 yr) experienced in strength training consumed either 20 mg androstenediol in a sublingual cyclodextrin tablet (Sl Diol) or placebo (Pl) separated by at least 1 wk in a randomized, double-blind, crossover manner. Blood samples were collected before supplementation and at 30-min intervals for 3 h after supplementation. Serum hormone concentrations did not change with Pl. Serum androstenedione concentrations were increased ( P < 0.05) above baseline (11.2 ± 1.1 nmol/l) with Sl Diol from 60 to 180 min after intake and reached a peak concentration of 25.2 ± 2.9 nmol/l at 120 min. Serum free testosterone concentrations were increased from 86.2 ± 9.1 pmol/l with Sl Diol from 30 to 180 min and reached a peak concentration of 175.4 ± 12.2 pmol/l at 60 min. Serum total testosterone concentrations increased above basal (25.6 ± 2.3 nmol/l) from 30 to 180 min with Sl Diol and reached a peak concentration of 47.9 + 2.9 nmol/l at 60 min. Serum estradiol concentrations were elevated ( P < 0.05) above baseline (0.08 ± 0.01 nmol/l) from 30 to 180 min with Sl Diol and reached 0.14 ± 0.02 nmol/l at 180 min. These data indicate that sublingual cyclodextrin androstenediol intake increases serum androstenedione, free testosterone, total testosterone, and estradiol concentrations.


2015 ◽  
Vol 8 ◽  
pp. CMED.S27700 ◽  
Author(s):  
Entesar O.A. El Saghier ◽  
Salah E. Shebl ◽  
Olfat A. Fawzy ◽  
lhab M. Eltayeb ◽  
Lamya M.A. Bekhet ◽  
...  

Background The association between type 2 diabetes mellitus (T2DM) and low total serum testosterone (LST) has been identified in several cross-sectional studies. Objectives To assess the prevalence of androgen deficiency and erectile dysfunction (ED) and their relation to glycemic control within a sample of Egyptian men with T2DM. Research Design and Methods A cross-sectional study including 70 men having T2DM. Their ages ranged from 30 to 50 years. They were evaluated for symptoms of androgen deficiency and ED, using a validated Arabic-translated Androgen Deficiency in Aging Males questionnaire and five-items version of the International Index of Erectile Function-5, respectively. Total testosterone (TT), glycated hemoglobin (HbA1c), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin were measured for all study subjects. Penile hemodynamics was assessed using penile duplex study for subjects who gave history of ED. Results LST was found in 40% of studied men, and 92.9% of them reported overt symptoms of androgen deficiency. ED was detected in 85.7% of those with LST, as opposed to 31.0% of those with normal TT ( P < 0.000). TT was lower in diabetic men with ED compared to those without ED (12.04 ± 5.36 vs 17.11 ± 7.11 nmol/L, P < 0.001). Significant negative correlation was found between TT and age, body mass index, waist circumference, systolic and diastolic blood pressures, and HBA1c ( P < 0.00). FSH, LH, and prolactin levels were within the normal reference range in all subjects. HbA1c was higher in patients who had LST with ED, compared to those with normal TT and without ED. However, multivariate logistic regression analysis did not reveal a significant association between HBA1c and LST levels. Conclusion LST, symptoms of androgen deficiency, and ED are common in the studied sample of Egyptian men with T2DM. Inappropriately normal FSH and LH in face of LST may denote a state of hypogonadotropic hypogonadism. HBA1c was found to be more significantly associated with ED than with LST.


2005 ◽  
Vol 7 (3) ◽  
pp. 211-215 ◽  
Author(s):  
H. de Boer ◽  
L. Verschoor ◽  
J. Ruinemans-Koerts ◽  
M. Jansen

2018 ◽  
Vol 7 (4) ◽  
pp. 523-533 ◽  
Author(s):  
Mikkel Andreassen ◽  
Anders Juul ◽  
Ulla Feldt-Rasmussen ◽  
Niels Jørgensen

Objective Gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) are released from the pituitary gland and stimulate Leydig cells to produce testosterone and initiates spermatogenesis. Little is known about how and when the deterioration of semen quality occurs in patients with adult-onset gonadotropin insufficiency. Design and methods A retrospective study comprising 20 testosterone-deficient men (median age, 29 years) with acquired pituitary disease who delivered semen for cryopreservation before initiation of testosterone therapy. Semen variables and hormone concentrations were compared to those of young healthy men (n = 340). Results Thirteen of 20 patients (65%) and 82% of controls had total sperm counts above 39 million and progressive motile spermatozoa above 32% (P = 0.05). For the individual semen variables, there were no significant differences in semen volume (median (intraquartile range) 3.0 (1.3–6.8) vs 3.2 (2.3–4.3) mL, P = 0.47), sperm concentration 41 (11–71) vs 43 (22–73) mill/mL (P = 0.56) or total sperm counts (P = 0.66). One patient had azoospermia. Patients vs controls had lower serum testosterone 5.4 (2.2–7.6) vs 19.7 (15.5–24.5) nmol/L (P = 0.001), calculated free testosterone (cfT) 145 (56–183) vs 464 (359–574) pmol/L (P < 0.001), LH 1.5 (1.1–2.1) vs 3.1 (2.3–4.0) U/L (P = 0.002) and inhibin b (P < 0.001). Levels of FSH were similar (P = 0.63). Testosterone/LH ratio and cfT/LH ratio were reduced in patients (both P < 0.001). Conclusions Despite Leydig cell insufficiency in patients with acquired pituitary insufficiency, the majority presented with normal semen quality based on the determination of the number of progressively motile spermatozoa. In addition, the data suggest reduced LH bioactivity in patients with pituitary insufficiency.


2016 ◽  
Vol 34 (2) ◽  
pp. 136-143 ◽  
Author(s):  
Yi Ren ◽  
Xiaoguang Yang ◽  
Yu Zhang ◽  
Ying Wang ◽  
Xuezhi Li

Objectives Partial androgen deficiency of the aging male (PADAM) is characterised by a deficiency in serum androgen levels. Both electroacupuncture (EA) and mild moxibustion (MM) can raise serum testosterone levels in PADAM. We investigated the mechanisms underlying the use of EA and MM in a rodent model of PADAM. Methods Fifty rats received cyclophosphamide injection over 5 consecutive days to induce PADAM, which was verified by comparing total testosterone (TT) and free testosterone (FT) levels with 10 non-PADAM healthy control rats (CON). Successful modelling was confirmed in 43 of 50 rats, 40 of which were randomly divided into untreated (PADAM), EA-treated (PADAM+EA), MM-treated (PADAM+MM), and androlin (AD)-treated (PADAM+AD) groups (n=10 each). EA and MM were administered at BL23 and CV4 acupuncture points for 8 weeks, and no treatment was given to rats in the PADAM and CON groups. Serum levels of luteinising hormone (LH) and follicle-stimulating hormone (FSH), mRNA expression of cytochrome P450c17 (P450c17) and 3β-hydroxysteroid dehydrogenase 1 (3β-HSD1), and protein levels of cytochrome P450 side chain cleavage (P450scc), 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) and steroidogenic factor 1 (SF-1) were evaluated after 8 weeks. Results Both EA and mild MM significantly increased serum TT and FT levels with MM displaying superiority. P450scc, 17β-HSD3 and SF-1 protein expression, and P450c17 and 3β-HSD1 mRNA expression, were significantly increased and serum LH and FSH levels were significantly decreased in PADAM+EA and PADAM+MM relative to PADAM rats. Moreover, serum LH and FSH levels were significantly lower and 17β-HSD3 protein expression significantly higher in PADAM+MM relative to PADAM+EA rats. Conclusions EA and MM at the BL23 and CV4 acupuncture points appear to be effective treatments for PADAM, and MM displays superior efficacy to EA.


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