Biochemical predictors of structural hypothalamus-pituitary abnormalities detected by magnetic resonance imaging in men with secondary hypogonadism.

PURPOSE: Organic conditions underlying secondary hypogonadism (SH) may be ascertained by magnetic resonance imaging (MRI) of the hypothalamic-pituitary region that could not be systematically proposed to each patient. Based upon limited evidence, the Endocrine Society (ES) guidelines suggest total testosterone (T) < 5.2 nmol/L to identify patients eligible for MRI. The study aims to identify markers and their best threshold value predicting pathological MRI findings in men with SH. METHODS: A consecutive series of 609 men seeking medical care for sexual dysfunction and with SH (total T < 10.5 nmol/L and LH ≤ 9.4 U/L) was retrospectively evaluated. An independent cohort of 50 men with SH was used as validation sample. 126 men in the exploratory sample and the whole validation sample underwent MRI. RESULTS: In the exploratory sample, patients with pathological MRI findings (n = 46) had significantly lower total T, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prostate specific antigen (PSA) than men with normal MRI (n = 80). Receiver Operating Characteristics analysis showed that total T, LH, FSH and PSA are accurate in identifying men with pathologic MRI (accuracy: 0.62-0.68, all p < 0.05). The Youden index was used to detect the value with the best performance, corresponding to total T 6.1 nmol/L, LH 1.9 U/L, FSH 4.2 U/L and PSA 0.58 ng/mL. In the validation cohort, only total T ≤ 6.1 nmol/L and LH ≤ 1.9 U/L were confirmed as significant predictors of pathologic MRI. CONCLUSION: In men with SH, total T ≤ 6.1 nmol/L or LH ≤ 1.9 U/L should arise the suspect of hypothalamus/pituitary structural abnormalities, deserving MRI evaluation.

Enclomiphene citrate: A treatment that maintains fertility in men with secondary hypogonadism.

INTRODUCTION: Hypogonadism is an important issue among the male population. Treatments such as exogenous testosterone have become very popular. One of the adverse effects of testosterone is its suppression of fertility. This has lead to the use of alternative therapies such as selective estrogen receptor modulators (SERMs) that aim to correct hypogonadism without reducing fertility. Areas covered: The SERM, clomiphene citrate, which is approved by the FDA for the treatment of ovarian dysfunction, has been shown to have beneficial effects on male hypogonadism. Clomiphene citrate exists as a mixture of both the cis-isomer (zuclomiphene) and the trans-isomer (enclomiphene). The literature has suggested that most of the beneficial effects of clomiphene are due to the trans-isomer enclomiphene. Zuclomiphene contributes little to the intended outcomes. The purpose of this drug profile is to examine the available literature on the trans-isomer enclomiphene. Expert opinion: Enclomiphene has been shown to increase testosterone levels while stimulating FSH and LH production. Initial studies demonstrated that enclomiphene maintains the androgenic benefit of clomiphene citrate without the undesirable effects attributable to zuclomiphene. This article reviews the difficulties associated with the FDA approval of a new molecular entity related to the treatment of hypogonadism.