The Acne-Hormone Connection

Blame it on the hormonesfor your acne that is. Hormonal imbalances can lead to chronic acne and that once-a-month flare-up. But one woman's hormonal flare is another woman's means to a quick fix.

What is it about hormones that create such havoc with the skin? Androgen and estrogen balance creates harmony for the skin; sort of a biochemical Yin and Yang. Upset this delicate balancing act can lead to blemishes, galore.

Much Ado About Acne

Acne is not due to a single event but the result of multiple steps going "wrong". Acne is a disorder of keratinization, meaning the formation of the cells that line the gland beneath the skin's surface is dysfunctional.

Under normal circumstances the epithelial cells lining the neck of the sebaceous gland should invisibly exfoliate under normal conditions onto the skin's surface through the pore. But these cells have a sticky surface, causing them to form a plug and preventing spontaneous exfoliation within the gland.

At the same time the plug has formed, the androgens have stimulated the sebaceous glands to enlarge and make extra oil.

The P. acnes bacteria that live within these glands are essentially served a feast of oil. They proliferate.

The gland is plugged, the oils continue to form whether or not they are able to reach the skin's surface, more bacteria form and inflammation occurs.

This cycle continues until the gland can no longer contain itself, expanding under pressure until it pops beneath the skin's surface. These are the events that contribute to the formation of inflammatory or cystic acne.

Acne therapy is aimed at intervening with various steps in this chain of events to clear and prevent recurrences.

Hormonal intervention of acne is aimed at preventing androgens from stimulating sebaceous gland activity; reducing sebum formation and can help minimize pore visibility.

Did I say pore size? Believe it or not, fluctuating levels of progesterone during our menstrual cycle is directly associated with changing pore size throughout the month.

Progesterone causes fluid retention and tissue swelling. We are all familiar with premenstrual "bloating". You can thank progesterone for that monthly puffiness. As the levels of progesterone rise and the skin swells, the pores are effectively compressed shut. This has 2 effects; by day 26, your pores never looked so minimized. However, this tourniquet effect causes sebum to build up beneath the skin's surface contributing to the formation of extra monthly blemishes.

An interesting multicenter study (JAAD 2001;45:957-60) showed that almost half of all women do experience a premenstrual flare of acne. But it's women ages 33 and up who are most often affected.

Bemoaning Hormones

A bevy of hormones can cause acne to form. Hormones responsible for acne include testosterone (an androgen), anabolic steroids, gonadotropins, corticosteroids and ACTH. Stress increases circulating glucocorticosteroids and should be factored into the hormone driven flare-up.

The ovaries produce both estrogen and testosterone. In women, estrogen should be in much higher concentrations, masking the androgenic or "male" effects of testosterone.

All women produce androgens and these hormones are there for a reason. It is when androgens outweigh estrogen either through total amounts or genetic hypersensitivity to the mere presence of androgen that a problem may arise.

Androgens

What exactly do androgens do? Androgens activate sebaceous glands to make sebum, that oil on the skin that for some produces a healthy glow, for others, creates a chronic oil slick. Androgens begin to form at puberty.

Androgens are responsible for those masculine qualities; acne, hair loss and hirsutism (excess facial hair) as well as an increase in both facial and body hair.

It is essential to first understand what occurs hormonally during the course of a 28-day menstrual cycle to understand what role hormones play in monthly acne.

A very simplistic review of the menstrual cycles shows estrogen levels increasing over the first 14 days, (days 1-14), until ovulation. Once the egg is released from the ovary, the levels of estrogen drop precipitously.

Overlapping the estrogen peak, starting at approximately days 12-14, the level of progesterone begins to rise. Progesterone (essentially translating to "pro" gestational state) is essential for preparing and maintaining the uterine lining for a successful pregnancy. If fertilization does not occur and the egg does not implant, progesterone levels begin to fall, assuming a "regular" cycle, menstrual flow begins at day 28.

Progesterone is made in the adrenal glands. Progesterone has qualities of both androgens and estrogen. In the best scenario, natural progesterone competes with androgens, particularly when estrogen levels drop at ovulation, helping prevent androgens from exerting their effects upon the skin.

Women can either make too much testosterone (such as in polycystic ovary syndrome/PCOS); make too little estrogen to mask the testosterone or have a genetic predilection towards highly sensitive skin and hair follicle cells to "normal" levels of androgens. By far the most common cause of androgenic acne is this natural ultra sensitivity to androgens.

Birth Control Pills and Acne

Oral contraceptives essentially function to prevent ovulation (release of the egg from the ovary), which in 98.8% of cases prevents pregnancy. There are currently an estimated 65 million women worldwide on oral contraceptives, which make for approximately 6% of all women of reproductive age.

Birth Control Pills (BCPs) contain varying amounts of estrogen (Ethinyl Estradiol aka EE) and a derivative of synthetic progesterone known as a progestin. There are many forms of progestins. They are either derived directly from testosterone or from progesterone.

Why do BCPs help control acne? In order to treat acne hormonally, one of the following must occur to stop hormones from wreaking havoc with the skin. The treatment must either:

• Block the androgens from reaching the receptors.
• Reduce the level of circulating androgens in the bloodstream.
• Prevent the formation of the androgens in the first place.

Conveniently, oral contraceptives are capable of all three of these actions. All oral contraceptives are anti-androgenic. OCs increase sex hormone binding globulin (SHBG), which binds to androgens and literally prevent them from going anywhere. Sort of a sponge-action approach.

At the same time, the progestin component (the synthetic form of progesterone) of an oral contraceptive competes to bind to the androgen receptors.

All birth control pills decrease the levels of circulating total and free testosterone.

Oral contraceptives also help prevent the formation of active androgens. Testosterone must be converted to dihydrotestosterone (DHT) in order to be active. Birth control pills prevent the enzyme 5 alpha reductase from functioning. Without this enzyme, the conversion process is stopped. DHT is responsible for those undesirable skin changes such as acne formation, hair loss of the scalp and extra hair growth on the face and body.

Three factoids on Birth Control Pills:

• All are anti-androgenic
• All help reduce circulating levels of testosterone
• All help reduce acne for the majority of women

But, that said, some BCPs are better than others for addressing acne concerns in women.

What Makes A Good BCP For Acne Treatment?

The FDA has only given its approval for Ortho-Tricyclen to carry the indication for treating acne. This particular medication went through the rigorous testing and studies required to prove to the FDA that it indeed was beneficial for acne as well as its ability to be a quality oral contraceptive.

However, understanding that all OCs have some benefit to helping acne and that there are going to be those that are "better than others", one looks at both the level of Ethinyl Estradiol as well as the type of Progestin.

The Estrogen Component

What you're going to see listed on your BCP ingredient list is a form of estrogen and a progestin.

Since 1992, all estrogen used in oral contraceptives is ethinyl estradiol, (EE). Only the level of EE used varies in the pill. This may be a constant dose ranging from 20mcgm/day to as high as 50mcgm/day.

Phasic oral contraceptives vary the level of EE throughout the cycle (phasic BCPs may also vary progestins or only progestins throughout the cycle as well).

Remember that increasing the level of estrogen both increases the level of Sex Hormone Binding Globulin and masks the levels of testosterone. This is helpful in reducing acne. So the lower the level of EE in a birth control pill, the less useful it will be as an acne therapy. That is why BCPs recommended specifically to help with acne often have a higher level of EE, typically in the 30-35mcmg range.

The Progestin Component

Natural progesterone is difficult to manufacture, so synthetic forms similar in structure and action to natural progesterone are used in oral contraceptives. These are referred to as progestins.

Progestin can be derived from testosterone by the simple removal of a methyl group from the testosterone. This creates the derivative Norethindrone.

Progestin can also come from the addition of a methyl group to testosterone and is called Norgestrel.

Both Norethindrone and Norgestrel are structurally similar to progesterone but contain little androgenicity.

Norgestrel turns into Levonorgesterel, it's active form and has more progesterone activity making it more useful for women facing progesterone insufficiency conditions but more likely to be acne forming.

Norethindrone derived progestins also include Norethindrone Acetate, Ethynodiol Diacetate and Lynesterol (this is not available in the U.S.)

Levonorgesterel derived progestins also include Desogestrel, Norgestimate and Gestodene (this is not available in the U.S.).

You may see either Norethindrone or Levonorgesterel or one of their derivatives on your BCP ingredient insert.

The type of progestin used in a birth control pill can also factor into how beneficial it may be to help control acne flare-ups. Some progestins have less androgenic tendencies than others.

A quick word on Depo-Provera. This long-lasting depot form of progesterone (medroxyprogesterone acetate) has occasionally been associated with acne as a side effect, and should be considered by those who are already acne-prone. Discuss this concern with your prescribing physician.

The level of androgenicity (tendency to be acne causing from highest to lowest):

Levonorgesterel > Norethindrone > Gestodene > Desogestrel > Cyrproterone Acetate (not used in BCPs, but a major anti-androgenic medication)

Types Of Birth Control Pills

I get many questions related to which birth control one should be on to help either treat acne or those that may be notorious for flare-ups.

Most women are not going to have acne flare-ups caused by a "wrong choice" of BCP brand and there is no reason for everyone to give up their favorite oral contraceptive. But if you purposely trying to select a brand of BCP to address acne concerns, discuss the following with your physician:

Yasmin, Demulen 1/50, Ortho-TriCyclen, Brevicon, Modicon, Necon, Ortho Evra, Mircette.

Remember that delicate hormonal balance? It is not unheard of when starting any oral contraceptive (even those meant to help improve acne) that acne flares may occur over the first 3 months of treatment until your body has fully acclimated to the change. This is not something to always have to expect or fear, but is certainly not unexpected.

I do want to stress that I am not advocating that all women take oral contraceptives to help their acne. The use of oral contraceptives is not entirely without concern. OCs can cause blood clots (especially in smokers), high blood pressure, and stroke and of course there is the on-going debate as to its ability to help or hinder in breast and uterine cancer as well as heart disease.

Spiraling Down The Acne

Some women are turning to non-contraceptive anti-androgen options in the treatment of their acne. Spironolactone (brand name Aldactone) is a water pill (diuretic) used to help reduce water retention in addition to helping control high blood pressure.

Spironolactone has a curious molecular structure lending itself to mimic androgens. This unique architecture allows it to bind to the androgen receptor and block the true androgen from binding and triggering those undesirable "male" skin and hair traits.

The downside to Spironolactone use includes symptomatic low blood pressure, irregular menstrual cycles, spotting and higher levels of potassium in the bloodstream. Avoiding excessive binging on high potassium-containing foods like bananas is important.

For women who crave the benefits of an anti-androgen but want to be on oral contraceptives, or for those who want to be on a BCP but hate those extra few pounds of water retention that tend to go hand in hand, a new generation pill, Yasmin, may be a solution.

Yasmin contains the progestin Drospirenone that is very similar structurally to Spironolactone. Because of its resemblance to Spironolactone, Yasmin can help avoid those extra few pounds of weight gain and may be beneficial in addressing androgenic acne.

A stray pimple every month may not warrant the use of hormonal therapy. After all, the risks however small do exist. Also, the hassle may simply not be worthwhile. Women who truly suffer from androgenic acne will want to visit their physician for a complete work-up to rule out other medical conditions and to pursue an effective treatment plan.

Audrey Kunin, M.D.

(Any topic discussed in this article is not intended as medical advice. If you have a medical concern, please check with your doctor.)

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