What is the treatment for hypogonadism (low sex hormone levels)?

Treatment for Hypogonadism

Testosterone replacement therapy (TRT) is the primary treatment for male hypogonadism with confirmed low testosterone levels and corresponding symptoms, while hormone replacement therapy with estrogen and progesterone is recommended for female hypogonadism. 1, 2

Male Hypogonadism Treatment

Diagnosis Before Treatment

• Diagnosis requires both persistent specific symptoms (decreased libido, erectile dysfunction, reduced muscle mass, fatigue) and confirmed testosterone deficiency through biochemical testing 1
• Morning serum total testosterone measurements should be repeated to confirm low levels due to variability in assays 1
• Evaluate for primary (testicular) vs. secondary (hypothalamic-pituitary) hypogonadism to guide treatment approach 1

Treatment Options Based on Type and Goals

For Men Not Concerned with Fertility

• Testosterone Replacement Therapy (TRT) is first-line treatment for confirmed hypogonadism 1, 2
  • Transdermal testosterone gels are most commonly used 3
  • Injectable testosterone formulations (testosterone enanthate or cypionate) are effective, safe, practical, and inexpensive 2, 4
  • Long-acting injectable testosterone undecanoate is an option for patients who prefer less frequent administration 3

For Men Desiring Fertility

• Gonadotropin therapy is recommended for hypogonadotropic hypogonadism when fertility preservation is desired 2, 4
  • Human Chorionic Gonadotropin (hCG) alone may be sufficient in men with partial or previously treated gonadotropin deficiency 4, 5
  • Combined treatment with hCG plus human menopausal gonadotropin (hMG) is often needed for men with prepubertal hypogonadotropic hypogonadism 4
• Pulsatile GnRH therapy may be used for men with hypothalamic defects (e.g., idiopathic hypogonadotropic hypogonadism) 4
• Clomiphene citrate (off-label) may be considered to stimulate endogenous testosterone production while maintaining fertility 3, 5

For Adolescents with Delayed Puberty

• Testosterone may be used to stimulate puberty in carefully selected males with clearly delayed puberty 2
• Treatment should be monitored with X-rays of hand and wrist every six months to assess effect on bone maturation 2
• Gonadotropins are preferred over testosterone for adolescents with hypogonadotropic hypogonadism to stimulate testicular growth and preserve fertility potential 4

Monitoring During Treatment

• Regular monitoring of hematocrit, prostate-specific antigen, and lipid profiles is essential 1
• Bone mineral density testing should be considered for hypogonadal patients 1
• Evaluate for symptom improvement and potential adverse effects 1

Female Hypogonadism Treatment

• Estrogen replacement with progesterone is first-line therapy for premenopausal women with hypogonadism 1, 6
• Hormone therapy should be tailored based on whether hypogonadism occurred before or after puberty 1
• Transdermal hormone replacement therapy may be appropriate for both premenopausal and postmenopausal women 6
• For women with primary ovarian failure, hormone replacement therapy aims to normalize ovarian hormone levels 1

Lifestyle Modifications for All Patients

• Weight loss through low-calorie diets can improve testosterone levels in men with obesity-associated secondary hypogonadism 1
• Regular physical activity and exercise should be encouraged 1, 6
• Adequate nutrition, calcium and vitamin D supplementation, and smoking cessation are important supportive measures 6

Important Cautions

• TRT should not be used in men with age-related hypogonadism without confirmed low testosterone levels 2
• The European Association of Urology specifically recommends against using testosterone therapy in eugonadal individuals 6
• TRT may compromise fertility in men by suppressing the hypothalamic-pituitary-gonadal axis 1, 5
• Treating based on symptoms alone without laboratory confirmation is not recommended 6