From the Guidelines
Current guidelines for hypogonadism treatment recommend testosterone replacement therapy (TRT) for men with consistently low testosterone levels (typically below 300 ng/dL) who also display symptoms such as decreased libido, erectile dysfunction, fatigue, and reduced muscle mass. The American College of Physicians (ACP) suggests that clinicians discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual function 1. Treatment options include:
- Intramuscular injections (testosterone cypionate 50-200 mg every 1-2 weeks or testosterone enanthate 50-200 mg every 1-2 weeks)
- Transdermal preparations (testosterone gel 1-2% applied daily, delivering 50-100 mg)
- Testosterone patches (2-6 mg/day)
- Subcutaneous pellets (150-450 mg implanted every 3-6 months) Before initiating therapy, patients should undergo prostate cancer screening with PSA testing and digital rectal examination. During treatment, regular monitoring is essential, including testosterone levels, hematocrit, lipid profile, and PSA every 3-6 months in the first year, then annually. For women with hypogonadism, treatment typically involves estrogen replacement therapy, with dosing dependent on age and menopausal status. Premenopausal women may receive combined estrogen-progestin contraceptives, while postmenopausal women might use lower-dose hormone therapy. Treatment aims to restore hormone levels to physiological ranges, alleviating symptoms while minimizing side effects such as polycythemia, sleep apnea, or prostate issues in men, and maintaining bone health and sexual function in both sexes 1. The ACP also suggests that clinicians consider intramuscular rather than transdermal formulations when initiating testosterone treatment to improve sexual function in men with age-related low testosterone, as costs are considerably lower for the intramuscular formulation and clinical effectiveness and harms are similar 1. Additionally, the ACP recommends that clinicians reevaluate symptoms within 12 months and periodically thereafter, and discontinue testosterone treatment in men with age-related low testosterone with sexual dysfunction in whom there is no improvement in sexual function 1.
From the FDA Drug Label
1 INDICATIONS AND USAGE Testosterone gel 1. 62% is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone: • Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals • Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation
The current guidelines for hypogonadism treatment, as per the provided drug label, involve testosterone replacement therapy for adult males with conditions associated with a deficiency or absence of endogenous testosterone, including:
- Primary hypogonadism: due to testicular failure from various conditions
- Hypogonadotropic hypogonadism: due to gonadotropin or LHRH deficiency or pituitary-hypothalamic injury The recommended starting dose of testosterone gel 1.62% is 40.5 mg of testosterone applied topically once daily in the morning to the shoulders and upper arms, with dose adjustments based on pre-dose morning serum testosterone concentration 2.
From the Research
Current INS Guidelines for Hypogonadism Treatment
The current guidelines for hypogonadism treatment are focused on restoring normal testosterone levels and improving symptoms. The main treatment for male hypogonadism is testosterone replacement therapy (TRT) 3. However, alternative treatments such as clomiphene citrate (CC) and gonadotropins may be considered for certain patients.
Testosterone Replacement Therapy (TRT)
- TRT is the standard treatment for hypogonadism, but it has some disadvantages, such as suppressing fertility and potentially increasing the risk of prostate cancer 4.
- Transdermal application of testosterone gels is a common route of administration, while oral testosterone formulations may be associated with hepatic toxicity or short half-lives 3.
- Injectable testosterone formulations, including short-acting and depot formulations, are also available 3.
Alternative Treatments
- Clomiphene citrate (CC) is an alternative off-label therapy for hypogonadal males, particularly those who desire fertility or have hypogonadotropic hypogonadism 5, 4, 6.
- CC has been shown to increase testosterone levels and improve hypogonadal symptoms with few side effects 5, 6.
- Gonadotropins, such as human chorionic gonadotropin (hCG), may be used to stimulate testicular growth and spermatogenesis in patients with hypogonadotropic hypogonadism 3, 6.
- Aromatase inhibitors (AI) and selective androgen receptor modulators (SARMs) may be considered for patients with specific conditions, such as obesity or high prostate disease risk 3.
Special Considerations
- In young hypogonadal males who desire future fertility, alternatives to TRT, such as CC and hCG, may be preferred to avoid suppressing spermatogenesis 7.
- Patients with central hypogonadism may require alternative treatments, such as gonadotropins or CC, to stimulate testicular growth and spermatogenesis 4.