The efficacy of anastrozole in subfertile men with and without abnormal testosterone to estradiol ratios.

Background: Aromatase inhibitors (AIs), such as anastrozole, have shown effectiveness in treating oligoasthenozoospermia due to abnormal testosterone to estradiol (T/E2) ratio (T/E2 <10). However, its efficacy in subfertile men without abnormal T/E2 ratio (T/E2 >10) remained unevaluated. This retrospective study aimed to investigate whether patients with T/E2 ratio >10 could also benefit from anastrozole treatment. Methods: One hundred and five subfertile patients treated with 1 mg anastrozole daily were included, in which 62 patients had a T/E2 ratio of <10, and 43 patients had this ratio >10. Semen parameters and sex hormone levels (including FSH, LH, PRL, E2 and total T) were measured before and after a three-month treatment. T/E2 ratio and total progressive motility sperm count were calculated from these results. Results: Patients in both groups (T/E2 ratio <10 and >10) showed significant increase in sex hormone levels (FSH, LH and total T), T/E2 ratio and semen parameters (semen volume, sperm concentration, total sperm count, progressive motility and total progressive motility count). The changes of these parameters between two groups were comparable. A subgroup analysis comparing the effect of anastrozole on overweight and normal patients also showed no significant difference. Improvements in semen parameters were seen in some azoospermic and cryptozoospermic patients. Conclusions: The majority of subfertile men with and without abnormal T/E2 ratios responded to anastrozole treatment with significantly improved semen parameters and sex hormone levels. Anastrozole showed potential effectiveness in male subfertile patients with T/E2 >10, to be confirmed by future prospective, randomized, controlled studies.

Cadmium exposure is associated with testosterone levels in men: A cross-sectional study from the China National Human Biomonitoring.

BACKGROUND: Sex hormone disorders can cause adverse health consequences. While experimental data suggests that cadmium (Cd) disrupts the endocrine system, little is known about the link between Cd exposure and sex hormones in men. METHODS: We measured blood cadmium (B-Cd), urine cadmium (U-Cd), serum testosterone and serum estradiol in men aged ≥18 years old participating in the China National Human Biomonitoring program, from 2017 to 2018. Urine cadmium adjusted for creatinine (Ucr-Cd) and the serum testosterone to serum estradiol ratio (T/E2) were calculated. The association of Cd exposure to serum testosterone and T/E2 in men was analyzed with multiple linear regression models. RESULTS: Among Chinese men ≥18 years old, the weighted geometric mean (95% CI) of B-Cd and Ucr-Cd levels were 1.23 (1.12-1.35) µg/L and 0.53 (0.47-0.59) µg/g, respectively. The geometric means (95% CI) of serum testosterone and T/E2 were 18.56 (17.92-19.22) nmol/L and 143.86 (137.24-150.80). After adjusting for all covariates, each doubling of B-Cd level was associated with a 5.04% increase in serum testosterone levels (ß = 0.071; 95%CI: 0.057-0.086) and a 4.03% increase in T/E2 (ß = 0.057; 95%CI: 0.040-0.075); similar findings were found in Ucr-Cd. CONCLUSIONS: In Chinese men, Cd may be an endocrine disruptor, which is positively associated with serum testosterone and T/E2.

Role of testosterone to estradiol ratio in predicting the efficacy of recombinant human chorionic gonadotropin and testosterone treatment in male hypogonadism.

OBJECTIVE: We aimed to investigate the role of testosterone to estradiol ratio in predicting the effectiveness of human chorionic gonadotropin and testosterone treatments in male hypogonadism. METHODS: Thirty-six male patients with hypogonadotropic hypogonadism were included in the study. Seventeen (47.2%) patients received weekly recombinant human choriogonadotropin alpha (hCG) treatment (group-1) and 19 (52.8%) received testosterone replacement therapy (T treatment) every 21 days (group-2). Under these treatments, adequate frequency of morning erection (≥3/week), testosterone to estradiol ratio (T/E), and testicular volume changes were analyzed. RESULTS: The mean age of the patients was 28.5 ± 8.7 years. When the frequency of morning erection (≥3/week) was specified as adequate, the cut-off value for effective T/E ratio was found to be 12.0 (sensitivity 93.8%, specificity 90.0%). There was no significant difference between the treatment groups in terms of total testosterone levels, T/E ratio, or frequency of morning erections (≥3/week) (p > 0.05). However, there was a statistically significant difference between the groups in terms of median left-right testicular volume in favor of group-1 (p < 0,05). CONCLUSION: In patients with hypogonadism who are under treatment, elevated estradiol-induced erectile dysfunction symptoms may persist even if serum testosterone levels are normal. Testosterone to estradiol ratio can be used as a predictive value in the effective treatment of hypogonadotropic hypogonadism with hCG and T.

Testosterone and depressive symptoms during the late menopause transition.

BACKGROUND: The menopause transition is associated with an increased risk of depression. While the mechanisms behind this increased risk are not well understood, the changing perimenopausal hormonal environment has been hypothesized to play a role. The current study examined the potential influence of testosterone and the ratio of testosterone to estradiol as a potential contributor to depressed mood in the menopause transition. METHODS: Fifty non-depressed perimenopausal women ages 45-55 were recruited for this study. Once every 3 weeks, for a total of four times, the women completed the Centre for Epidemiological Studies-Depression (CES-D) scale for the measurement of depressive symptoms and provided a first-morning urine sample for the measurement of urinary testosterone as well as estrone-3-glucuronide (E1G), a urinary metabolite of estradiol. The week-to-week and mean effects of testosterone, E1G, and the testosterone/E1G ratio on CES-D score were examined. Self-reported sleep quality and vasomotor symptoms were also assessed at each of the four time points. RESULTS: Testosterone levels rose with increasing months since last menstrual period associated with testosterone levels (ß(SE) = 175.3(63.2), p = .006), though this effect was moderated by body mass index (p for the interaction = .001) such that overweight women showed a less pronounced increase over time. Past and current smokers also had higher testosterone levels compared to never smokers. Week-to-week testosterone/E1G ratio was positively associated with CES-D score (ß(SE) = 1.57(0.76), p = .041) but not sleep quality or vasomotor symptoms (ps > .05). Mean testosterone/E1G ratio was also positively associated with vasomotor symptom bother (ß(SE) = 0.14(0.06), p = .018) and poorer sleep quality (ß(SE) = - 0.34(0.09), p = .0001). CONCLUSION: These results suggest that, within the context of the menopause transition, times that are characterized by a higher testosterone-to-estradiol ratio may be associated with higher depressive symptoms. Perimenopausal women with a higher average ratio of testosterone relative to estradiol may also experience more sleep difficulties and vasomotor symptom bother.

Role of testosterone to estradiol ratio in predicting the efficacy of recombinant human chorionic gonadotropin and testosterone treatment in male hypogonadism

ABSTRACT Objective: We aimed to investigate the role of testosterone to estradiol ratio in predicting the effectiveness of human chorionic gonadotropin and testosterone treatments in male hypogonadism. Materials and methods: Thirty-six male patients with hypogonadotropic hypogonadism were included in the study. Seventeen (47.2%) patients received weekly recombinant human choriogonadotropin alpha (hCG) treatment (group-1) and 19 (52.8%) received testosterone replacement therapy (T treatment) every 21 days (group-2). Under these treatments, adequate frequency of morning erection (≥3/week), testosterone to estradiol ratio (T/E), and testicular volume changes were analyzed. Results: The mean age of the patients was 28.5 ± 8.7 years. When the frequency of morning erection (≥3/week) was specified as adequate, the cut-off value for effective T/E ratio was found to be 12.0 (sensitivity 93.8%, specificity 90.0%). There was no significant difference between the treatment groups in terms of total testosterone levels, T/E ratio, or frequency of morning erections (≥3/week) (p > 0.05). However, there was a statistically significant difference between the groups in terms of median left-right testicular volume in favor of group-1 (p < 0,05). Conclusion: In patients with hypogonadism who are under treatment, elevated estradiol-induced erectile dysfunction symptoms may persist even if serum testosterone levels are normal. Testosterone to estradiol ratio can be used as a predictive value in the effective treatment of hypogonadotropic hypogonadism with hCG and T.

Outcomes of anastrozole in oligozoospermic hypoandrogenic subfertile men.

OBJECTIVE: To determine whether the change in sperm parameters in subfertile hypoandrogenic men treated with anastrozole is correlated to the magnitude of increase in testosterone (T) to estrogen ratio in men responding to treatment. DESIGN: Retrospective study. SETTING: Male fertility clinic. PATIENT(S): The study group consisted of 86 subfertile hypoandrogenic men with low T/estradiol (E2) ratio (n = 78) or a prior aversive reaction to clomiphene citrate (n = 8). INTERVENTION(S): All patients were treated with 1 mg anastrozole daily, administered orally. MAIN OUTCOME MEASURE(S): Hormone analysis and semen analysis before and after treatment were performed. Hormone analysis included measurements of total T, E2, sex-hormone binding globulin, albumin, FSH, and LH, and bioavailable T was calculated. Total motile sperm count was calculated from the semen analysis. RESULT(S): In all, 95.3% of patients had an increased serum T and decreased serum E2 after treatment with anastrozole. Sperm concentration and total motile counts improved in 18 of 21 subfertile hypoandrogenic oligozoospermic men treated with anastrozole. In these men the magnitude of total motile count increase was significantly correlated with the change in the T/E2 ratio. No improvement was seen in semen parameters of men with azoospermia, cryptozoospermia, or normozoospermia at presentation. CONCLUSION(S): Approximately 95% of men with hypoandrogenism responded with improved endocrine parameters, and a subset of oligozoospermic men (approximately 25% of all patients) displayed significantly improved sperm parameters. In that subset, increase in sperm parameters was correlated with the change in the T/E2 ratio, which argues for a physiologic effect of treatment.