Endocrine Abstracts

A 53-year-old male was referred to the endocrinology outpatient clinic due to elevated levels of gonadotropins and testosterone (LH 11.7 IU/l, reference range 1.7-8.6 IU/l; FSH 17.7 IU/l, reference range 1.5-12.4 IU/l; testosterone 40.9 nmol/l, reference range 6.68-25.70 nmol/l; free testosterone 712.7 pmol/l, reference range 163-473 pmol/l) noted during an annual urologic check-up. No spermiogram was performed, and testicular ultrasound showed no abnormalities. The patient reported no physical complaints other than chronic fatigue and reduced energy since experiencing an occupational burnout 2 years ago. He was not on any medications but regularly consumed Withania somnifera (Ashwagandha) and Tinospora cordifolia. These herbs are commonly used in alternative medicine to alleviate anxiety, stress, and fatigue. MRI imaging showed no signs of pituitary lesions. Despite discontinuation of the herbal remedies, gonadotropin and testosterone levels remained elevated even after 3 months. Withania somnifera contains substances such as steroid lactones, phytosterols, and alkaloids. Phytosterols, resembling cholesterol, can serve as precursors to steroid hormone synthesis. According to the Memorial Sloan Kettering Cancer Center database, Withania somnifera may increase testosterone levels for this reason, as demonstrated in a randomized, double-blind, placebo-controlled study. The cause of elevated gonadotropins remained unclear and requires further investigation. Tinospora cordifolia also contains phytosterols, but data on its effect on steroid hormone synthesis is limited to animal models. Although no definitive effect on steroid hormone synthesis has been proven, it cannot be excluded. Determining a causal relationship between drug use and observed adverse drug reactions involves intrinsic evidence (temporal relationship with drug exposure, dechallenge and rechallenge if applicable, exclusion of other causes, pathophysiological plausibility) and extrinsic evidence (well-documented comparable cases in drug information, pharmacovigilance databases, systematic clinical or epidemiological studies, and possibly case reports). In this case, a clear temporal relationship was observed between the intake of herbal remedies and elevated testosterone levels. Other likely causes were ruled out, and the pathophysiology involving phytosterols as steroid hormone precursors is plausible. The absence of intrinsic evidence is due to the lack of a positive dechallenge, as gonadotropin and testosterone levels remained high after discontinuation. However, extrinsic evidence from a randomized, double-blind, placebo-controlled study, although rare for alternative remedies, supports the conclusion that hypergonadotropic hypergonadism may be caused by Withania somnifera.