It depends. If FH is due to a reversible condition, treatment consists of removing the offending agent: for instance, one of the drugs listed in Table 1 that affect the physiology of the hypothalamic-pituitary-testicular (HPT) axis.
For opioids, probably the most frequent pharmacologic cause of FH, resuming activity of HPT axis requires significant time. If the patient is young and affected by severe symptoms, TRT is justified and should be continued if associated with symptomatic improvements. A 2017 study showed that TRT in patients affected by opioid-induced hypogonadism was associated with an increase in median T of 262.5 ng/dL and an improvement of common hypogonadal symptoms that included libido, erectile function, body composition, and quality of life (P <0.05).17
Other reversible causes of FH include obesity and type 2 diabetes (T2DM) (Table 1). Studies have demonstrated that indirect measures, such as lifestyle changes in obese individuals or improved hemoglobin A1c (HbA1c) control in individuals with T2DM, effectively increase serum TT concentrations and reduce erectile dysfunction (ED). For instance, weight loss is associated with (proportionate) increases in TT18 and improvement in ED,19 and improved glycemic control is associated with increases in T levels.20
The decision of whether to treat individuals with FH who are unable to modify their lifestyle can be informed by recent studies that support TRT effectiveness21 and cardiovascular22 safety. The Testosterone trials (T-trials) showed that older men with FH who are receiving TRT experience a (modest) improvement in libido, sexual satisfaction, and sexual activity and a lesser improvement in erectile function (compared to libido). The T-trials also showed that hemoglobin increases by ~1 g/dL with the correction of baseline anemia.23 TRT in older men also increases volumetric trabecular bone mineral density (BMD), estimated bone strength, and areal BMD increase.24 However, T-trials did not show a significant positive effect on vitality and physical or cognitive function.21
The Transverse study, which was published in 2023 and powered to assess the cardiovascular (CV) safety of TRT, suggests that this treatment is not associated with increased CV risk for 2 years of treatment.22 Based on these results, if the presence of FH is confirmed by biochemistry and clinical presentation, a physician can initiate a course of TRT after discussing the benefits and side effects with the patient. The patient should be monitored and TRT discontinued if no response is present after 6 to 12 months.
Alternative treatments to lifestyle modifications and TRT, for instance use of clomiphene or human chorionic gonadotropin (HCG), have not been tested in properly powered clinical trials and are not recommended in clinical practice.