Hormones – Basics: Sex Hormones, DHT & Endocrinology in Men

Sex Hormones – Overview

Sex hormones are steroid hormones synthesized from cholesterol that play a central role in development, reproduction, and sexual function. Although they are classically divided by sex, all sex hormones occur in both sexes – merely in different concentrations and with different biological effects.

In men, testosterone is the dominant sex hormone. About 95 percent of it is produced in the Leydig cells of the testes; a small proportion comes from the adrenal cortex. Testosterone governs the development of male sexual characteristics during fetal development and puberty, regulates libido, muscle growth, bone density, and erythropoiesis, and is essential for sperm production. Estrogens also occur in men and arise mainly through peripheral aromatization of testosterone; they play a physiological role in bone metabolism, lipid profile, and – to a lesser extent – spermatogenesis. A relative excess of estrogen can lead to gynecomastia.

The production of sex hormones is regulated by a hierarchically organized hormone axis: the hypothalamus releases GnRH (gonadotropin-releasing hormone) in a pulsatile rhythm, which prompts the pituitary gland to secrete LH (luteinizing hormone) and FSH (follicle-stimulating hormone). LH stimulates testosterone production in the Leydig cells; FSH acts on the Sertoli cells and is essential for spermatogenesis. Testosterone, in turn, has an inhibitory effect back on the hypothalamus and pituitary gland (negative feedback mechanism), thereby maintaining hormonal balance.

Dihydrotestosterone (DHT)

DHT is a biologically highly potent androgen formed from testosterone by the enzyme 5-alpha reductase. It binds to the androgen receptor with roughly five times higher affinity than testosterone itself and thus exerts a markedly stronger androgenic effect – with a shorter dissociation time from the receptor, which allows for precise tissue regulation.

Developmentally, DHT is indispensable: during fetal development it governs the formation of the external male genitalia; during puberty it is responsible for the development of facial and body hair, the tendency toward acne through stimulation of the sebaceous glands, and the development of the prostate. Two isoforms of 5-alpha reductase are known: type 1 is found predominantly in the liver and skin, type 2 primarily in the prostate, testes, and hair follicles.

DHT is clinically significant above all because of its role in two common conditions. In genetically susceptible hair follicles, DHT leads to androgenetic alopecia through progressive miniaturization of the follicles. In the prostate, DHT stimulates glandular growth and is a key factor in the development of benign prostatic hyperplasia (BPH). Pharmacological 5-alpha reductase inhibitors – particularly finasteride (type-2-specific) and dutasteride (inhibiting both type 1 and type 2) – are used specifically to lower DHT levels and treat both conditions.

Endocrinology in Men

Male endocrinology deals with the function and disorders of all hormone-producing glands and their effects on the male organism. It overlaps clinically with urology and andrology, since many endocrine disorders have a direct impact on sexual function, fertility, and body composition.

The central hormone-producing structures in the male system are the hypothalamus as the superordinate regulatory center, the pituitary gland (anterior pituitary) as the executive organ for hypothalamic control signals, the testes as the primary source of testosterone and the site of spermatogenesis, and the adrenal cortex as the site of production of androgen precursors such as DHEA.

Typical endocrinological topics in men include hypogonadism (primary or secondary), pubertal disorders (delayed or precocious puberty), fertility disorders due to hormonal dysregulation, pituitary disorders such as prolactinoma or GH excess, as well as the hormonal changes that come with aging (andropause). Monitoring an ongoing hormone therapy – such as testosterone replacement therapy – is also a core area of male endocrinology.

Diagnosis is carried out through serum hormone analyses (basal and stimulated levels), imaging (testicular ultrasound, pituitary MRI if a central cause is suspected), and, where necessary, genetic testing. Hormonal disorders in men are primarily treated by specialized endocrinologists or andrologists; close interdisciplinary collaboration at the interface with urology is often required.