Androgens and Acne

Acne is a common skin disease and it usually begins during the teenage years. It is mostly found on the face but it usually affects other parts of the skin such as the back and upper part of the chest where sebaceous follicles are highly concentrated.

Therefore, acne affects the pilosebaceous units which include hair follicles and sebaceous glands.

Acne causes seborrhea or scaly, red skin; comedones such as whiteheads and blackheads; pustules and papules. In severe cases acne nodules, cysts and acne scars will appear on the skin.

These acne lesions are triggered by a number of causes. However, there are two root causes of acne: androgens and acne-causing bacteria. These two causes cause a cycle of acne breakouts that may continue well into adulthood.

What Are Androgens?

Androgens are steroid hormones that control the development and sustenance of male characteristics such as male sex organs and secondary sex characteristics.

However, androgens are not only produced in males, they are also produced in females. In females, androgens are used to synthesize the main group of female sex hormones called estrogens.

The major example of androgens is testosterone. It is produced in the testicles of males, ovaries of females and in the adrenal glands.

Androgens serve a number of functions in humans. Some of its major functions are:

• Development of male sex organ and characteristics – The first androgens are produced from the Leydig cells which differentiate at week 8 of fetal development. The released androgens masculinize the male fetus by stimulating the development of the penis and scrotum. Later in life, androgens also stimulate the production of spermatozoa during puberty
• Inhibition of fat deposition – Androgen inhibits fat deposition by reducing the ability of some fat cells to accumulate lipids. Androgens also produce this effect by increasing the levels of epinephrine and norepinephrine. These endogenous substances stimulate the breakdown of lipids. Both of these effects are the reason why males have less body fat than females
• Increase in muscle mass – Androgens enlarge skeletal muscle cells through a cell line called myoblast. This action increases muscle tissues and is responsible for the greater muscle mass in male than female
• Regulation of brain activity and structure – Androgens can influence the human activity and behavior and is also suspected to account for the differences in the structures of male and female brains. Because neurons are sensitive to androgens, these hormones can influence libido and aggression.

Testosterone and Metabolites

Testosterone is an anabolic steroid and a hormone produced in both male and female.

While testosterone is the primary male sex hormone, females are more sensitive to it. Males produce 20 times more testosterone than females because they use it up at a far greater rate. Testosterone is responsible for increments in bone mass, muscle mass and body hair.

From childhood to puberty, the levels of androgens rise in the body. This causes increased oiliness of the skin and hair among other things.

By the time, male and female hit puberty, androgens cause the enlargement of the sebaceous glands. This enlargement results in the increased production of sebum and greater oiliness of the skin. The first breakout of acne occurs around this time.

The level of testosterone then reduces during adulthood. This is the reason acne clears away in most people during their mid-twenties.

There are 2 major metabolites of testosterone. These are dihydrotestosterone and estradiol.

DHT is found in male sex organs and in the skin especially in the hair follicles. While 7% of testosterone is converted to DHT, only 0.3% is converted to estradiol.

DHT is an androgen while estradiol has no androgen properties but it is responsible for female sex characteristics. As an androgen, DHT is 5 times more potent than testosterone.

Testosterone exerts its effects on androgen receptors either directly or through DHT. When converted to estradiol, it activates estrogen receptors.

While testosterone is produced in both male and female, it is produced more in males. Estrogen, the chief female sex hormone is also produced in both sexes but more is produced in females. Both of these sex hormones counteract each other. Therefore, estrogen is often referred to as an anti-androgen hormone.

How Androgens Cause Acne

The 4 androgens that are most relevant to the skin are testosterone, DHEA, DHT and androstenedione.

These androgens are mostly synthesized at sites other than the skin. Therefore, they reach the skin via the blood. However, men synthesize testosterone in the skin while women produce both DHT and testosterone in the skin.

Although DHEA is a weak androgen, it is the one with the highest serum concentration of the androgens. However, it is converted to androstenedione and more potent androgens such as testosterone and DHT by the cells of the sebaceous glands.

While androstenedione and testosterone increase sebum secretions, the main effects of DHT on skin cells, besides increasing sebum production, are to increase beard growth and cause scalp hair loss.

First Androgens

Androgens act at androgen receptors found all over the skin. Androgen receptors are found in the cells of keratin, sebaceous glands, sweat glands, hair follicles and skin endothelium. These receptors are found in the cytoplasm of cells where they form complexes with heat shock proteins such as hsp 56, hsp 70 and hsp 90.

When androgens bind to these receptors, the heat shock proteins are dissociated from the receptors.

The number of androgen receptors can only be increased in two of the cell lines found in the skin. These are the dermal fibroblasts and the sebocytes.

Androgens will not only increase the number of androgen receptors found in sebocytes, they will also increase the number of sebocytes. When receptor up-regulation and sebocyte proliferation occur, the condition is called cutaneous hyperandrogenism.

Several studies have identified a strong link between excessive androgen production in the skin and skin disorders such as acne and alopecia in men. Other studies have identified testosterone and DHT as the chief androgens causing this effect.

In females, DHT is the most important androgen causing acne. In a study measuring plasma levels of the 4 androgens, there were elevated DHT levels in women with acne than in women without the skin condition.

What androgens primarily do is to increase the number of the cells of the sebaceous gland.

With increased production of sebocytes, the sebaceous glands grow and are enlarged. Therefore, the glands produce more cells to secrete sebum. This causes the production of excess sebum which is responsible for the increased oiliness of acne skins especially among adolescents.

Androgens do not indiscriminately trigger sebocyte proliferation all over the skin. In fact, this effect is only observed on certain areas of the skin and these areas are the parts of the skin mostly affected by acne.

Facial sebocytes are mostly affected by androgen stimulation of sebocyte proliferation. Therefore, acne breakouts are mostly concentrated in the face.

When excess sebum is pushed up to the skin surface, some of it go rancid and congeal in skin pores. This clogs those pores and directly leads to the formation of acne lesions such as whiteheads, blackheads and pimples.

The excess sebum that reaches the skin surface changes the nature of the skin.

Then Bacteria

Besides increasing the oiliness of the skin and attracting dirt to stick to the skin and clog the pores further, excess sebum is the ideal growth environment for acne-causing bacteria.

In the presence of excess sebum, acne-causing bacteria such as Propionibacterium acnes and Staphylococcus epidermis colonize the skin surface in increasing numbers.

These bacteria change the nature of the skin further; they disrupt the pH balance; they further increase sebum production; and then they cause an abnormal cycle of inflammation which produces the inflammatory lesions observed during moderate and severe acne breakouts.

Oral Contraceptives, Anti-androgens and Acne

There are different approaches to treating acne caused by the excessive production and stimulatory effects of androgens. The 3 treatment goals are to:

• Reduce the plasma levels of androgens in order to reduce the amount of these hormones that get to the skin
• Inhibit the metabolism and interconversion of androgens in order to lower the production of DHT and testosterone from DHEA
• Block androgen receptors in order to block the effects of androgens on sebocytes and other skin cells

Women may have especially high levels of circulating androgens for a number of reasons. One such reason is physiological states such as pregnancy or menopause when the production of estradiol, a natural anti-acne hormone, falls off.

High androgen levels can also be caused by underlying disease conditions such PCOS (polycystic ovarian syndrome) or Cushing’s syndrome. Both diseases lead to excessive production of androgens which may continue silently with little or no other symptoms.

To combat these hormonal changes, anti-androgens are usually prescribed.

The major anti-androgen medications used in the treatment of acne include oral contraceptives, oral corticosteroids, Finasteride and fluatmide.

These drugs should be combined with other anti-acne remedies for faster results.

Oral Contraceptives

Oral contraceptives or birth control pills work by reducing the levels of androgens and/or increasing the levels of estrogen.

Oral contraceptives containing estrogen or ethinylestradiol and/or the anti-androgenic progestin hormones are effective. 

Of the progestin anti-androgenic hormones, cyproterone acetate is the most effective. It works by inhibiting androgen receptors and by blocking the conversion of DHEA to other androgens.

Oral Corticosteroids

For men and women with hyperandrogenism or other diseases which causes abnormal androgen levels, low dose oral corticosteroids are recommended.  The most popular drug in this class is prednisolone.

Corticosteroids suppress the production and release of androgens from the adrenal gland.

Spironolactone is an oral synthetic corticosteroid commonly used to treat hypertension because of its diuretic effect. It can also be used to treat acne. It works by inhibiting androgen receptors, the syntheses of androgens and the conversion of testosterone to DHT.

It is mostly useful for treating adult acne in women.

Finasteride

Finasteride is used to treat alopecia especially male pattern baldness. Because it blocks the conversion of testosterone to DHT, it is also used to treat acne especially in men.

However, Finasteride is a weaker anti-androgen than cyproterone and spironolactone.

Flutamide

Flutamide is an oral, non-steroidal anti-androgen used in the treatment of prostate cancer. It is competitive antagonist to testosterone and DHT at androgen receptors. Therefore, it is useful as an anti-acne medication.