Androgens (male hormones present in both males and females) increase the production of skin oil, which can in turn cause an increase in both general acne and cystic acne. Generally speaking, the more androgens one has in their blood and skin, the more severe their acne may become.
Research has found that people with cystic acne often have high levels of androgens in their blood, which causes increased skin oil production and more severe acne.
There are three main hormonal treatments for nodulocystic acne:
Cystic acne, medically referred to as nodulocystic acne, is an especially severe form of acne that includes two main types of acne lesions: nodules and cysts.
Both nodules and cysts are large (over 5mm in diameter), red, painful lesions that develop deep within the skin, and can take weeks, months, or even years to heal. Without proper treatment, they will not heal on their own and will likely cause permanent scarring.
Hormones play a role in the development of all types of acne. The main hormones associated with the development of acne in both males and females are androgens, which are male hormones that help control the development of sexual characteristics during puberty in both males and, to a lesser extent, females. There are three types of androgens that influence acne:
- Dihydrotestosterone (DHT) - the most potent androgen
- Testosterone - another powerful androgen
- Dehydroepiandrosterone sulfate (DHEA-S) - a weak androgen that the body can convert into the more powerful testosterone or DHT when needed
In both males and females, beginning at puberty, these hormones are produced by the sex organs and also the adrenal glands, which are located near the kidneys.
After production, the hormones travel in the blood to various areas of the body, including to the skin. When androgens reach the skin, they enter special cells called sebocytes, which are located in skin oil-producing glands called sebaceous glands, and stimulate the glands to produce more skin oil, called sebum. The more androgens present in the skin, the more sebum that is produced, and generally speaking, increased amounts of sebum result in more acne and more severe lesions, like nodules and cysts.1–4
Hormones Contribute to Both Regular Acne and Nodulocystic Acne
Whether it’s regular acne or severe, nodulocystic acne, hormones are required for acne to form. Let’s start with learning the three main steps in acne development since all acne starts the same way and hormones are always involved.
Human skin is covered in tiny hairs. Acne begins when the opening of a hair follicle becomes clogged with skin cells, at which point it is called a microcomedone, better known simply as a clogged pore. This clog causes the sebum, which normally drains to the surface, to become trapped inside the pore.
How are hormones involved? It is unclear what triggers this initial clog. Traditionally, scientists thought an increase in hormones caused it, but more recent research has shown us that it is likely inflammation that is at fault. To what degree hormones are involved is still under investigation.
When sebum is trapped inside the pore, it accumulates. At this stage, the acne lesion is called a comedone, more commonly known as a whitehead or blackhead, depending on the appearance of the lesion. As the sebum continues to accumulate, it blocks the opening of the pore. When this occurs, the amount of oxygen inside the pore decreases. A type of bacteria called P. acnes thrives in areas abundant in sebum and with little oxygen. Consequently, when the sebum builds up inside the pore, this bacteria begins to reproduce rapidly.
How are hormones involved? Androgens play a major role in this step of acne development because they control the production of sebum. More androgens normally mean more sebum.
The body sees the growth of P. acnes inside the pore as “invaders” and sends “troops” in the form of inflammatory cells to get rid of the excessive bacteria. The inflammatory cells cause inflammation and can make the area red and sore. The “battle” between the inflammatory cells and bacteria weakens the pore wall. This weakened pore wall, combined with the growing pressure caused by the buildup of sebum, ruptures. The rupture releases sebum, skin cells, and bacteria into the surrounding skin, which causes even more inflammation. At this point a sore, inflamed pimple, called a papule or pustule is formed. If the pore completely explodes, nodules and cysts may form.
How do hormones relate? Androgens play a role in this step because they directly control the production of sebum. More sebum increases pressure inside the pore, causing the pore to expand and rupture.
Clearly, many factors influence acne development, but a major one is the production of sebum. Androgens increase sebum production, and therefore can lead to acne lesions, including nodulocystic acne lesions.1–3
People with Nodulocystic Acne Have Increased Androgens
Scientists have performed two studies to look at whether people with people with nodulocystic acne, possess elevated androgen levels. They have determined that this is in fact the case.5,6
A 1983 study published in The New England Journal of Medicine measured the levels of two hormones in 59 female and 32 male nodulocystic acne patients. All 91 patients were resistant to conventional acne treatments. The two hormones tested were DHEA-S and 17-hydroxyprogesterone. DHEA-S is an androgen that is known to increase sebum levels directly. 17-hydroxyprogesterone is a different hormone also produced by the adrenal glands that the body converts into either DHEA-S or testosterone when it needs more androgens. The researchers found that 80% of females and 81% of males had elevated DHEA-S levels, while 14% of females and 34% of males showed elevated 17-hydroxyprogesterone levels. The researchers concluded, “[M]ost patients with therapeutically resistant cystic acne have androgen excess and that lowering elevated [DHEA-S] results in improvement or remission of acne in most instances.”5
A 1985 study published in Clinical and Experimental Dermatology measured the levels of testosterone and other androgens in 42 female and 17 male acne patients. The researchers divided the participants into three groups, based on acne severity. Although the researchers did not explicitly say how they classified acne severity, it is likely that the group labeled as “severe acne group” consisted of patients with nodulocystic acne. There were 19 females and 5 males in the severe acne group. To perform this study, the researchers obtained blood samples from all patients to measure the level of testosterone and other androgens in the blood. They found that testosterone was on average 22.4% higher in the people with acne. However, this number was calculated using all patients with acne, including those who had mild acne. Unfortunately, the authors of the study did not report whether the levels of testosterone were even higher in people with nodulocystic acne. They did report that DHT was elevated in all severe acne patients. However, from this study, it appears that DHT is increased in nodulocystic acne patients.6
Hormonal Treatments for Nodulocystic Acne
One option for nodulocystic acne treatment is hormonal therapy. There are three main types of hormonal therapies: cortisone shots, which both males and females can use, as well as oral contraceptives and spironolactone, which only females can take.
- Cortisone shots are steroid hormones that are injected directly into a nodule or cyst and can quickly reduce inflammation and initiate healing.
- Oral contraceptives, otherwise known as the birth control pill, is an effective hormonal treatment that females can use, but can come with side effects. In addition to preventing pregnancy, oral contraceptives can calm the effects of androgens and treat acne. They can only be used by females, because in males they can cause feminization symptoms, including breast growth and sexual dysfunction. These also are not appropriate for pregnant women since they can feminize a male fetus.
- Spironolactone is a drug called an anti-androgen, which prevents androgens from working. It can be prescribed on its own or alongside an oral contraceptive. Doctors usually only prescribe spironolactone to women because it can also cause feminization and sexual dysfunction symptoms in men.7 Like oral contraceptives, spironolactone can come with side effects.
There are two studies demonstrating the effectiveness of hormonal medications to treat nodulocystic acne, both of which showed that hormonal treatment significantly reduced nodulocystic acne symptoms.5,8
A 1983 study published inThe New England Journal of Medicine examined the effect of dexamethasone (corticosteroid) and Demulen (oral contraceptive) to decrease the levels of DHEA-S in males and females. To perform this study, the researchers provided dexamethasone to 32 men with nodulocystic acne, and either dexamethasone, Demulen, or both to 59 female nodulocystic acne patients daily for six months. After the six-month treatment period, the hormonal treatments cleared the nodulocystic acne in 97% of females and 81% of males. More specifically, of the 32 male patients taking dexamethasone, 8 were cleared of their acne; 18 saw a reduction in acne, and 6 noticed no change. Of the 43 female patients taking only dexamethasone, 26 cleared their acne; 15 experienced a reduction in acne, and 2 saw no change. Of the 4 women taking only Demulen, 3 eradicated their acne, and 1 saw a reduction in acne. Of the 12 women taking a combination of dexamethasone and Demulen, 8 cleared their acne, and 4 saw at least a 50% reduction. The researchers concluded, “[M]ost patients with therapeutically resistant acne have androgen excess and lowering [DHEA-S] results in improvement or remission of acne in most instances.”5
A 1984 study published in the British Journal of Dermatology examined the effect of spironolactone on 26 acne patients, of which at least 3 experienced nodulocystic acne. To perform it the patients were given either 100 milligrams (mg) or 200mg of spironolactone per day for three months. The researchers found that of the patients taking 100mg per day, 67% of females and 83% of males demonstrated marked improvement of their acne. The patients who took 200mg daily had the strongest response to the treatment, and 3 patients with nodulocystic acne who had not responded to other treatments significantly improved on a daily 200mg dosage. The researchers concluded that spironolactone may be a useful treatment for general and nodulocystic acne.8
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- Androgen, <https://en.wikipedia.org/wiki/Androgen>
- Toyoda, M. & Morohashi, M. Pathogenesis of acne. Med Electron Microsc 34, 29–40 (2001).
- Degitz, K. et al. Pathophysiology of acne. JDDG 5, 316–323 (2007).
- Reingold, S. The relationship of mild hirsutism or acne in women to androgens. Arch Dermatol 123, 209–212 (1987).
- Marynick, S. et al. Androgen Excess in Cystic Acne. N Engl J Med 308, 981–986 (1983).
- Lawrence, D. et al. Elevated free testosterone concentration in men and women with acne vulgaris. Clin Exp Dermatol 11, 263–273 (1986).
- Tobechi, L. et al. Hormonal treatment of acne in women. J Clin Aesthet Dermatol 2, 16–22 (2009).
- Goodfellow, A. et al. Oral spironolactone improves acne vulgaris and reduces sebum excretion. Br J Dermatol 111, 209–214 (1984).