Testosterone therapy does not affect coagulation in male hypogonadism: a longitudinal study based on thrombin generation.

CONTEXT: Testosterone therapy has been variably associated with increased thrombotic risk but investigations of global coagulation in this setting are lacking. OBJECTIVE: To compare global coagulation of hypogonadal men before (T0) and 6 months after (T1) starting testosterone replacement therapy (TRT), and healthy controls. DESIGN: Observational prospective cohort study. SETTING: Two tertiary endocrinological ambulatory care centers. PATIENTS: Thirty-eight men with hypogonadism (mean age 55, SD 13) and 38 age-matched healthy controls. INTERVENTIONS: Thrombin generation assay (TGA) was performed at T0 and T1 in hypogonadal men and in controls. TGA is an in vitro procedure based on the continuous registration of thrombin generation and decay under conditions mimicking the process that occurs in vivo. MAIN OUTCOME MEASURES: The following TGA parameters were recorded: lag-time; thrombin-peak concentration; time-to-reach the peak, velocity index and endogenous thrombin potential (ETP), the latter representing the total amount of thrombin generated under the driving forces of procoagulants opposed by the anticoagulants. PC, antithrombin, factor (F)VIII, and fibrinogen were assessed. RESULTS: No changes of TGA parameters were observed between T0 and T1. Hypogonadal men displayed significantly higher ETP, fibrinogen, and significantly lower antithrombin levels both at T0 and T1 compared to controls. Thrombin-peak of hypogonadal men was significantly higher than controls at T0 but not at T1. ETP and antithrombin were correlated with testosterone levels. CONCLUSIONS: Hypogonadal men display a procoagulant imbalance detected by increased thrombin generation. Short-term TRT does not worsen global coagulation, suggesting that the treatment can be safely prescribed to men diagnosed with hypogonadism.

The association of hypogonadism with depression and its treatments.

According to World Health Organization estimates, 5% of the adult population worldwide suffers from depression. In addition to the affective, psychomotor and cognitive symptoms which characterize this mood disorder, sexual dysfunction has been frequently reported among men suffering from depression. The most common sexual manifestations are decreased libido, erectile dysfunction and orgasmic disorder. In addition, epidemiological studies have documented a reduction of testosterone concentrations in men with depression and, for these reasons, depressive disorders appear as one possible cause of male functional hypogonadism. Moreover, some largely used antidepressant medications can cause or worsen sexual complaints, thus depression and its treatments rise several andrological-relevant issues. The other way round, men with hypogonadism can manifest depressed mood, anxiety, insomnia, memory impairment which, if mild, may respond to testosterone replacement therapy (TRT). However, the prevalence of functional hypogonadism in depression, and of depressive symptoms in hypogonadal men, is not known. Severe depressive symptoms do not respond to TRT, while the effect of treating major depression on functional hypogonadism, has not been investigated. Overall, the clinical relevance of each condition to the other, as well as the physiopathological underpinnings of their relationship, are still to be clarified. The present review summarizes current evidence on the influence of testosterone on mood and of depression on the hypothalamic-pituitary-testis axis; the clinical association between male hypogonadism and depression; and the reciprocal effects of respective treatments.

Bone health in functional hypothalamic amenorrhea: What the endocrinologist needs to know.

In the original definition by Klinefelter, Albright and Griswold, the expression "hypothalamic hypoestrogenism" was used to describe functional hypothalamic amenorrhoea (FHA). Given the well-known effects of estrogens on bone, the physiopathology of skeletal fragility in this condition may appear self-explanatory. Actually, a growing body of evidence has clarified that estrogens are only part of the story. FHA occurs in eating disorders, overtraining, and during psychological or physical stress. Despite some specific characteristics which differentiate these conditions, relative energy deficiency is a common trigger that initiates the metabolic and endocrine derangements contributing to bone loss. Conversely, data on the impact of amenorrhoea on bone density or microarchitecture are controversial, and reduced bone mass is observed even in patients with preserved menstrual cycle. Consistently, oral estrogen-progestin combinations have not proven beneficial on bone density of amenorrheic women. Low bone density is a highly prevalent finding in these patients and entails an increased risk of stress or fragility fractures, and failure to achieve peak bone mass and target height in young girls. Pharmacological treatments have been studied, including androgens, insulin-like growth factor-1, bisphosphonates, denosumab, teriparatide, leptin, but none of them is currently approved for use in FHA. A timely screening for bone complications and a multidisciplinary, customized approach aiming to restore energy balance, ensure adequate protein, calcium and vitamin D intake, and reverse the detrimental metabolic-endocrine changes typical of this condition, should be the preferred approach until further studies are available.