Androgens play a part in the biology of gender by stimulating and controlling the development and maintenance of masculine characteristics. They are the sex steroids or hormones that produce changes in body shape and secondary sexual characteristics (such as hair and beard growth, penile growth) that are typical of men. Glands in the body produce hormones that circulate in the bloodstream to act on organs or tissues at another site. Androgens are also the mediators of terminal hair growth throughout the body. With sexual maturity during puberty, the androgens cause enlargement of vellus hairs to form terminal hair in the axilla and pubis in both sexes, and on the face, chest and extremities in men. This is termed as the development of the secondary sexual characteristics.

Androgens and Baldness in Men

In 400 BC Hippocrates noticed that castrated males, called eunuchs, did not become bald. He was the first to recognize the connection between hair loss and the sexual organs. This connection was later voiced out by Aristotle. In 1942, the studies of Hippocrates and Aristotle were continued with the work of Dr. James Hamilton. He discovered that certain male hormones (missing in eunuchs) were critical to the development of male pattern baldness. The time of castration was vital according to Dr. Hamilton, he observed that those who were castrated prior to puberty did not develop pattern baldness (the medical term for male or female pattern balding) and that by injecting testosterone castrated men can suffer pattern baldness. He also concluded that there was a genetic predisposition present in the androgen where certain preconditions can cause the progression of baldness.

However it is now known that it is more specifically the male hormone dihydrotestosterone (DHT) which is converted from the enzyme testosterone by the enzymes 5 alpha reductase which contributes to Androgenetic Alopecia in those who are genetically predisposed. It is interesting to note that individuals with a deficiency in 5 alpha reductase do not develop Androgenetic Alopecia. This is because the body is unable to convert the testosterone into dihydrotestosterone.

It has been documented that without the presence of androgens, scalp hair grows constitutively while body hair growth is inhibited; and with androgen activity, genetically predisposed persons develop a definite pattern of scalp alopecia manifested as miniaturization of scalp hair follicles. Miniaturization of hair can be described as the transformation of large terminal hairs (thick pigmented hairs) into fine vellus hairs. Vellus hair are very soft and short hairs that grow in most places on the human body in both sexes. It is usually less than 2cm long and the follicles are not connected to sebaceous glands.

There is no satisfactory explanation for the contradictory influence of androgens on hair at different body sites. Pre-pubertal pubic, axillary, beard, and chest Vellus hair follicles respond to androgens by growing into terminal hairs. The contradiction exists because the same androgens transform the pigmented terminal hairs on the scalp into non-pigmented fuzzy hairs. This is because Dihydrotestosterone causes a reduction in protein synthesis by inhibiting adenyl cyclase in the hair bulb; the result is shorter and finer hair, referred to as miniaturized hair.

Pathogenesis of Androgenetic Alopecia

Although the clinical presentation is different in men and women, the underlying cellular processes causing AGA are thought to be similar. AGA is caused by androgens in both men and women. Androgens are produced in men by the testes and adrenal glands. In women, androgens are produced by the ovaries and adrenal glands. Androgens produced peripherally by endocrine-sensitive hair follicles and sebaceous glands also contribute significantly to circulating androgens in both men and women. All men and women with AGA have normal levels of circulating androgens.

The androgen dihydrotestosterone (DHT), a potent metabolite of the androgen testosterone (T), causes a gradual, progressive shrinkage in the length and caliber of genetically programmed hair follicles. This process is called miniaturization. Miniaturization results from shortening of the anagen phase and a decrease in the sit of the dermal papilla and volume of matrix cells. Consequently, each succeeding hair cycle results in production of smaller, finer hairs which contribute less to the overall appearance and density of the hair.

These biochemical events occur at the cellular level of the hair follicle. Because the dermal papilla is highly vascular, it is continuously bathed in circulating androgens. It has been demonstrated that the dermal papilla is rich in androgen receptors and is the primary target of androgen action. Cells in genetically programmed hair follicles contain the enzyme 5-Alpha-reductase. 5-Alpha Reductase converts Testosterone into the more potent DHT. 5-Alpha Reductase is found in higher quantities in the scalp follicles of affected men and women. There are two distinct forms of 5 alpha -Reductase, referred to as types 1 and 2, which differ in their tissue distribution. Both types are capable of producing DHT from testosterone, but they have different biochemical and pharmacologic properties. The genes for 5-alpha reductase have been mapped to chromosome 5. Both are deemed important in pattern baldness development.

Androgen receptors in the cells of the dermal papilla bind with circulating DHT (dihydrotestosterone), forming androgen-receptor complexes. These complexes are presented to binding sites on the DNA in the cell nuclei of the dermal papilla. Modified DNA sends messages via messenger RNA to the matrix cells, creating proteins to carry out the androgen effects of miniaturization on the hair follicle.

Loss of scalp hair in pattern baldness occurs gradually over many years in an orderly pattern and depends on factors within each follicle. Studies using both plucked hairs and scalp biopsies have demonstrated an increased DHT production in balding as against non-balding scalps.

Androgen Receptor

The androgen receptor is a member of the steroid receptor family of nuclear transcription factors. This family is a group of structurally related nuclear transcription factors that mediate the action of steroid hormones. The steroid receptor family includes three other receptors including the glucocorticoid receptor, the mineralocorticoid receptor, and the progesterone receptor.

Androgen receptors allow the body to respond appropriately to androgens. The receptors are scattered in the different parts of the body. This where they bind to androgens and become activated. By turning the genes on or off as necessary, the androgen receptor helps direct the development of male sexual characteristics.

Interconversion of Androgens

Any steroid precursor can get metabolized into estrogen. Many steroids in the steroid line or derivatives lead to estrogens one way or another. Five known isoenzymes catalyze the 17ß-hydroxysteroid dehydrogenase reaction that controls the interconversion of estrone and estradiol and of testosterone and androstenedione. The key enzyme in the production of estrogens is aromitase. If a line is drawn through the aromatase-catalyzed reactions, all of the estrogens will be on one side of the line, and the anabolic and androgenic steroids will be on the other side. This means that aromitase can be considered as a gatekeeper that influences the relative dominance of estrogenic versus anabolic/androgenic influences within the steroidal hormonal system.

The easiest way to find out how these enzyme systems work is to observe them in action. Measuring dehydro epiandrosterone (DHEA), progesterone, testosterone and estradiol before and after any supplementation with a steroid precursor allows us to observe the resulting shifts in hormone ratios that allows us to infer enzyme activities.