Table 1.

Comparison of therapeutic options for hypogonadism. Aromatase inhibitors, AI; Food and Drug Administration, FDA; gonadotropin-releasing hormone, GnRH; hypothalamic–pituitary–gonadal, HPG; randomized controlled trial, RCT; testosterone replacement therapy, TRT.

Therapy	Mechanism of Action	Side Effects	Benefits	Risks
Testosterone Replacement Therapy	Administers exogenous testosterone through various formulations (oral, intramuscular, transdermal, subdermal, buccal, and nasal).	Associated with potential risks, including cardiovascular events, impaired fertility, obstructive sleep apnea, and erythrocytosis.	Supported by substantial long-term RCT evidence; FDA-approved to treat men with hypogonadism.	Risk of significant adverse effects, particularly erythrocytosis and infertility.
Aromatase Inhibitors	Inhibit the enzymatic conversion of testosterone to estradiol, reducing negative feedback on the HPG axis.	Common side effects include nausea, headache, and hot flashes. Less frequent effects include libido changes and elevated liver enzymes. Decreased bone mineral density has been reported.	Improves hypogonadal symptoms and fertility outcomes without causing major side effects.	Potential risk of decreased estradiol interfering with bone metabolism and associated symptoms; lack of long-term RCT data.
Tamoxifen	Blocks estrogen’s negative feedback on the hypothalamus and pituitary gland, leading to increased GnRH production, which subsequently boosts endogenous testosterone secretion.	Potential adverse effects include weight gain, sexual dysfunction, hot flashes, and neurocognitive impairment; rare reports of infertility and idiopathic gynecomastia.	Improves hypogonadal symptoms and fertility outcomes without significant side effects or suppression of estradiol.	Requires a functional HPG axis; lacks robust RCT evidence.
Clomiphene		Reported side effects include headaches, visual disturbances, dizziness, gynecomastia, and testicular enlargement; rare instances of azoospermia have been documented.	Improves hypogonadal symptoms and fertility outcomes without significant side effects or suppression of estradiol; particularly promising for men with obesity-related hypogonadism or those prioritizing fertility preservation; cost-effective compared to TRT.	Requires a functional HPG axis; high-quality RCTs and long-term follow-up data are needed to fully establish its safety and efficacy.