New Biomarkers to Evaluate Hyperandrogenemic Women and Hypogonadal Men

Androgens can have variable effects on men and women. Women may be evaluated for androgen excess for several reasons. Typically, young premenopausal women present with clinical symptoms of hirsutism, alopecia, irregular menses, and/or infertility. The most common cause of these symptoms is polycystic ovary syndrome. After menopause, even though ovaries stop producing estrogen, they continue to produce androgen, and women can have new onset of hirsutism and alopecia. Laboratory evaluation involves measurement of the major ovarian and adrenal androgens. In women, age, phase of the menstrual cycle, menopausal status, obesity, metabolic health, and sex hormone-binding proteins significantly affect total-androgen levels and complicate interpretation. This review will summarize the clinically relevant evaluation of hyperandrogenemia at different life stages in women and highlight pitfalls associated with interpretation of commonly used hormone measurements. Hypogonadism in men is a clinical syndrome characterized by low testosterone and/or low sperm count. Symptoms of hypogonadism include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men. Hypogonadism is observed rarely in young boys and adolescent men. Based on the defects in testes, hypothalamus, and/or pituitary glands, hypogonadism can be broadly classified as primary, secondary, and mixed hypogonadism. Diagnosis of hypogonadism in men is based on symptoms and laboratory measurement. Biomarkers in use/development for hypogonadism are classified as hormonal, Leydig and Sertoli cell function, semen, genetic/RNA, metabolic, microbiome, and muscle mass-related. These biomarkers are useful for diagnosis of hypogonadism, determination of the type of hypogonadism, identification of the underlying causes, and therapeutic assessment. Measurement of serum testosterone is usually the most important single diagnostic test for male hypogonadism. Patients with primary hypogonadism have low testosterone and increased luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Patients with secondary hypogonadism have low testosterone and low or inappropriately normal LH and FSH. This review provides an overview of hypogonadism in men and a detailed discussion of biomarkers currently in use and in development for diagnosis thereof.