From the Guidelines
Androgen resistance in males should be treated with testosterone supplementation for partial resistance, and estrogen replacement therapy after gonadectomy for complete resistance, with a multidisciplinary approach to management. This condition, also known as androgen insensitivity syndrome (AIS), occurs due to mutations in the androgen receptor gene, resulting in varying degrees of feminization despite having XY chromosomes. According to the Endocrine Society's clinical practice guidelines update in 2015 1, testosterone replacement therapy (TRT) can have beneficial effects on sexual function, insulin sensitivity, osteoporosis, muscle strength, and symptoms of frailty in hypogonadal men. For partial androgen resistance, testosterone supplementation may be beneficial, typically starting at 50-100mg intramuscularly every 2-4 weeks or daily transdermal applications of 50-100mg, with dosage adjusted based on clinical response. Complete androgen insensitivity often requires estrogen replacement therapy after gonadectomy, usually with estradiol 1-2mg daily.
Key considerations in management include:
- Psychological support, as patients with androgen resistance may have specific psychosocial needs related to gender identity
- Genetic counseling for family planning
- Regular follow-up to monitor hormone levels, bone density, and overall health, as these patients have increased risk of osteoporosis
- A multidisciplinary approach to management, involving endocrinologists, urologists, and mental health professionals. The annual incidence of hypogonadism is 20% in men in their 60s and 30% in men in their 70s, highlighting the importance of proper diagnosis and treatment 1.
From the Research
Androgen Resistance in Males
- Androgen insensitivity syndrome (AIS) is a disorder characterized by peripheral androgen resistance due to androgen receptor mutations in subjects with 46 XY karyotype 2, 3.
- The severity of hormone resistance determines the wide spectrum of phenotypes, which can be complete, partial, or mild 2, 3.
- Clinical suspicion of AIS can arise at birth or at pubertal age, and diagnosis can be achieved through genetic testing, including karyotype examination and androgen receptor sequencing 2.
- Laboratory tests showing elevated LH and testosterone levels despite mild or absent virilization may be helpful in diagnosing AIS 2, 3.
Management of Androgen Resistance
- The management of AIS requires a multidisciplinary team consisting of physicians, surgeons, and psychologists to support the patient and their family on gender identity choices and subsequent therapeutic decisions 2.
- Treatment depends on the phenotype and social sex of the individual, and open issues in management include decisions on sex assignment, timing of gonadectomy, fertility, psychological outcomes, and genetic counseling 3.
- In cases of androgen deficiency, treatment aims to restore normal physiological levels of testosterone using exogenous testosterone, and patients should be followed closely to monitor their response to treatment 4, 5, 6.
Testosterone Replacement Therapy
- Testosterone replacement therapy can restore normal serum testosterone concentrations and relieve symptoms in most hypogonadal men 5, 6.
- Selection of the treatment method depends on the patient's preference and advice from the physician, and dose adjustment is possible with most delivery methods 6.
- The use of hepatotoxic androgens should be avoided, and testosterone treatment can induce reversible suppression of spermatogenesis 6.