Androgen

Overview

Androgens are a group of hormones that play a role in male traits and reproductive activity. Present in both males and females, the principle androgens are testosterone and androstenedione.

Androgens may be called "male hormones," but don't let the name fool you. Both men's and women's bodies produce androgens, just in differing amounts. In fact, androgens have more than 200 actions in women, and they are present in higher amounts than estrogens.

The principal androgens are testosterone and androstenedione. They are, of course, present in much higher levels in men and play an important role in male traits and reproductive activity. Other androgens include dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S).

In a woman's body, one of the main purposes of androgens is to be converted into the female hormones called estrogens.

Androgens in Women

In women, androgens are produced in the ovaries, adrenal glands and fat cells. In fact, women may produce too much or too little of these hormones––disorders of androgen excess and deficiency are among the more common hormonal disorders in women.

In women, androgens play a key role in the hormonal cascade that kick-starts puberty, stimulating hair growth in the pubic and underarm areas. Additionally, these hormones are believed to regulate the function of many organs, including the reproductive tract, bone, kidneys, liver and muscle. In adult women, androgens are necessary for estrogen synthesis and have been shown to play a key role in the prevention of bone loss, as well as sexual desire and satisfaction.

Androgen-Related Disorders

High Androgen Levels

Excess amounts of androgens can pose a problem, resulting in such "virilizing effects" as acne, hirsutism (excess hair growth in "inappropriate" places, like the chin or upper lip) and thinning of hair on the head (balding).

About 10 percent of women with high levels of a form of testosterone called "free" testosterone have polycystic ovary syndrome (PCOS), characterized by irregular or absent menstrual periods, infertility, blood sugar disorders (prediabetes and type 2 diabetes), and, in some cases, symptoms like acne and excess hair growth. Most women with PCOS are overweight or obese, though a small percentage have a normal body weight. Left untreated, high levels of androgens, regardless of whether a woman has PCOS or not, are associated with serious health consequences, such as insulin resistance and diabetes, high cholesterol, high blood pressure and heart disease.

In addition to PCOS, other causes of high androgen levels (called hyperandrogenism) include congenital adrenal hyperplasia (a genetic disorder affecting the adrenal glands that afflicts about one in 10,000 to one in 18,000 Americans, about half of whom are women) and other adrenal abnormalities, and ovarian or adrenal tumors. Medications such as anabolic steroids, occasionally abused by body builders and other athletes for performance enhancement, can also cause hyperandrogenic symptoms.

Low Androgen Levels

Low androgen levels can be a problem as well, producing effects such as low libido (interest in or desire for sex), fatigue, decreased sense of well-being and increased susceptibility to bone loss, osteoporosis and fractures. Because symptoms like flagging desire and general malaise have a variety of causes, androgen deficiency, like hyperandrogenism, often goes undiagnosed.

Low androgen levels may affect women at any age, but most commonly occur during the transition to menopause, or "perimenopause," a term used to describe the time before menopause (usually two to eight years). Androgen levels begin dropping in a woman's 20s, and by the time she reaches menopause, have declined 50 percent or more from their peak as androgen production declines in the adrenal glands, and the mid-cycle ovarian androgen boost lessens or evaporates altogether.

Further declines in the decade following menopause indicate ever-decreasing ovarian function. For many women, the effects of this further androgen decline include aggravation of hot flashes and accelerated bone loss. These effects may not become apparent until the women are in their late 50s or early 60s.

Treatment for Low Androgen Levels

Combination estrogen/testosterone medications are available for women in both oral and injected formulations. Small studies find they are effective in boosting libido, energy and well-being in women with androgen deficiencies, as well as providing added protection against bone loss. One study showed some increased risks of breast and endometrial cancer, along with several other adverse effects, from one oral form of combined estrogen and testosterone, but these risks have not been demonstrated with other forms of treatment.

Testosterone is also an effective treatment for AIDS-related wasting and is undergoing studies for treating premenstrual syndrome (PMS) and autoimmune diseases. Women with PMS may have below-normal levels of testosterone throughout the menstrual cycle, suggesting that a testosterone supplement may help, but such treatments have not been proven effective.

Diagnosis

Your androgen levels may be normal, too high (hyperandrogenism) or too low (hypoandrogenism). A health care professional can assess whether your symptoms suggest abnormal levels and can order a blood test to measure hormone levels. But results from blood tests are often misleading and may not be conclusive because there is no agreement on just what constitutes "normal" androgen levels in women. Plus, levels fluctuate depending on a woman's age, the timing of her menstrual cycle and her menopausal status. Further, many standard laboratory tests, optimized for measuring testosterone in men, may not be sensitive enough to accurately measure women's levels. As a result, it is easier to diagnose androgen levels that are too high, rather than levels that are too low.

If you suspect you have a hyperandrogenic condition, it is important to seek a diagnosis and develop and begin a treatment plan. Hyperandrogenism can produce bothersome cosmetic symptoms like unwanted hair on your upper lip and chin. Psychologically, the clinical manifestations of hyperandrogenemia (persistent acne, excess facial or body hair, thinning of hair on the scalp and obesity) can be devastating to young girls and women of reproductive age and may contribute to feelings of low self-esteem, anxiety, depression and antisocial behavior. Women with excessive, uncomfortable sexual tension may also have high levels of androgens.

Hyperandrogenic conditions are also associated with serious health problems like insulin resistance (a precursor to diabetes), diabetes and heart disease.

Hyperandrogenic syndromes often go undiagnosed, even though symptoms may be treated. For example, you may be treated for acne, without being evaluated for glucose tolerance or asked about menstrual regularity. It may be up to you to tie together some of your hyperandrogenic symptoms and ask for a more integrated evaluation and treatment approach.

The signs and symptoms of hyperandrogenism are:

• Hirsutism (excess facial or body hair)
• Persistent acne and/or oily skin
• Alopecia (thinning hair on the head)
• Insulin resistance
• Acanthosis nigricans (rough, darkly pigmented areas of skin)
• High blood pressure
• Low HDL cholesterol ("good cholesterol") and high LDL cholesterol ("bad cholesterol")
• Obesity around the mid-abdomen
• Irregular or absent periods or frequent skipped cycles
• Enlargement of the clitoris
• Deep or hoarse voice

If your symptoms include irregular or absent periods, you may have polycystic ovary syndrome (PCOS)––the most common condition associated with hyperandrogenism. The menstrual irregularity indicates infrequent or absent ovulation, making PCOS a leading cause of female infertility, which is often treatable.

Some women with hyperandrogenism may experience spontaneous ovulation, and pregnancies may occur. However, women with high androgen levels also have an increased risk of miscarriage.

Hyperandrogenic symptoms may also be caused by a genetic disease called congenital adrenal hyperplasia (CAH). Severe cases can result in such extreme effects as genital malformation and virilization (facial hair, acne) at a young age.

Milder cases may look a lot like PCOS, with symptoms possibly including facial hair, irregular periods and high blood pressure. Women with mild CAH may also be shorter than their parents, vulnerable to infections and have a somewhat "masculine build," with square shoulders and narrow hips.

A thorough medical history and physical examination provide the most important initial diagnostic information. Laboratory tests usually serve to confirm the presence of hyperandrogenemia, a medical term meaning too much androgen in the blood. A blood test for total and free testosterone may be ordered, as well as a lipid profile (to measure cholesterol levels), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin and a fasting glucose test. Several endocrine function tests may also be ordered to determine the site(s) of abnormal androgen secretion, such as DHEA or its sulfate form, DHEAS. Thyroid tests are usually included in the evaluation. Inflammation is also a component of PCOS, so a physician may choose to measure some inflammatory markers as well.

Hormone therapy (HT), which consists of either estrogen and progestin (sometimes referred to as hormone replacement therapy, or HRT) or estrogen-only therapy (ET), and birth control pills containing estrogen, are other treatment options. Oral estrogens boost levels of sex hormone binding globulin (SHBG), a protein made in the liver that binds testosterone and estrogen. This reduces levels of free testosterone, which may be triggering symptoms. Glucocorticoids (cortisone), which are often prescribed for asthma or inflammation, can also suppress production of androgens.

Androgen Deficiency

Androgen levels in women peak during their 20s. Then a decline in daily production begins that continues throughout a woman's life. The only time a sudden drop-off in androgen levels occurs is in women who have their ovaries removed (about half of all androgens are produced in a woman's adrenal glands and half in her ovaries). By the time a woman reaches menopause, blood androgen levels are about half of what they were at their peak.

Low androgen levels in women during their reproductive years, as well as following menopause, result in three noticeable symptoms: low libido, fatigue and a reduced sense of well-being. Low androgen levels also have been linked to bone loss and osteoporosis (a disease that causes thin, fragile bones), possibly explaining the phenomenon of excessive bone loss in some women who go through ovarian failure or surgical removal of the ovaries.

Low sex drive and vaginal dryness are two common symptoms experienced by some women during the transition to menopause, making sex uncomfortable or painful. These changes have been related to low estrogen as well as low androgen levels. If you recognize any of the following changes, you should see your health care professional to discuss your concerns.

1. Have you noticed that it takes longer for your vagina to become lubricated before or during sex?
2. Have you noticed that the amount of vaginal lubrication is less?
3. Do you have discomfort or pain during vaginal penetration?
4. Do you have sex less frequently?
5. Do you and/or your partner wish you had sex more often?
6. Are you less responsive to sexual stimulation?
7. Do you have difficulty reaching orgasm?
8. Has your desire for sex decreased?

To diagnosis androgen deficiency, your health care professional will consider symptoms such as low libido and fatigue. Other conditions that can cause similar symptoms will also need to be ruled out. Blood tests for testosterone and SHBG will likely be part of your evaluation. SHBG binds to testosterone, making it less available for influencing cellular actions. SHBG levels can vary dramatically in response to oral estrogen therapy following menopause or to oral contraceptives. In some women, SHBG changes are modest and have minimal effect on free androgen levels, while in others, it can increase greatly and give rise to lowered sex drive (undesirable) or reduced free testosterone and a resulting decrease in side effects such as acne and hirsutism (desirable)

Blood testing for testosterone in hypoandrogenic women is problematic. Health care professionals have not reached a consensus about what constitutes low levels in women, and levels at the lower end of the female range are difficult to measure with many commercially available laboratory tests. For this reason, Endocrine Society Clinical Practice Guidelines recommend against making a formal diagnosis of androgen deficiency.

The causes of androgen deficiency are varied. The most common cause of low androgen is aging. If your symptoms bother you, you may want to talk to your health care professional about androgen replacement.

Androgen deficiency may be a particular problem if:

• Your ovaries have been removed
• You have undergone early menopause (generally defined as menopause occurring prior to age 40)
• You have Turner's syndrome, a genetic growth disorder that occurs in about one in 2,000 girls that arises when one, or part of one, of the two X chromosomes is missing (two X's code for a female, an XY for a male). This is a condition in which the ovaries fail to develop.
• You are postmenopausal
• You have undergone chemotherapy or radiation treatment for cancer

Other conditions associated with low testosterone include hypothalamic amenorrhea (absence of menstrual periods resulting from excessive dieting and exercising) and hyperprolactinemia (characterized by high levels of prolactin, the hormone that drives milk production when a woman breastfeeds). Additionally, a variety of pituitary gland tumors are also associated with low production of testosterone, as well as other hormones.

Sometimes there is no obvious cause of androgen deficiency. Otherwise healthy women of reproductive age can suffer from low androgens, which can be confirmed with blood tests and after other potential causes of low libido and fatigue are eliminated.

To exclude other potential causes of low libido and fatigue, your health care professional may ask you about past psychological or relationship problems and check for other potential causes of fatigue, such as depression, hypothyroidism and iron deficiency.

If you are postmenopausal and are taking hormone replacement therapy (estrogen alone or an estrogen/progestin combination), your estrogen levels may be checked to ensure your estrogen dosage is high enough. Therapy with oral estrogens (oral estradiol) and conjugated estrogens (conjugated equine estrogen or synthetic conjugated estrogens) or esterified estrogens can be difficult because oral estrogens are metabolized to estrone, which can be difficult to measure, and conjugated and esterified estrogens are largely composed of estrogenic compounds not measured in commercially available hormone tests. Transdermal estrogens (patches, gels, injections, etc.), are more easily assessed with commercial laboratory tests.

Treatment

Androgen disorders cannot be cured but they can be treated, usually with medication. If you are overweight, losing as little as 5 to 10 percent in body weight can restore fertility and decrease hirsutism in some women with androgen excess.

Treatment may also include oral contraceptives. Keep in mind if you are of reproductive age, the right oral contraceptive choice can reduce hyperandrogenic symptoms, while the wrong one can make them worse. When you hear the term oral contraceptives or birth control pills, it most often refers to "combination pills"—pills that contain both estrogen and progestin. The estrogen used is almost always ethinyl estradiol in varying doses, but numerous progestins are used, also in varying doses. The key is the type of progestin included. Some progestins can mimic androgens and make symptoms worse, but some avoid this problem, allowing the estrogen in birth control pills to raise levels of sex hormone binding globulin (SHBG), reducing blood levels of free testosterone and improving symptoms. Standard-dose birth control pills, which contain 35 mcg of ethinyl estradiol, may be preferable in these circumstances to pills containing lower doses of ethinyl estradiol. Talk to your health care professional about a pill formulation with progestins that do not have an androgen effect and which are known to elevate SHBG, such as norgestimate, drospirenone or desogestrel.

For some women, the most bothersome symptoms of high levels of androgen are acne and hirsutism. For women with such symptoms, spironolactone (Aldactone or Spironol) may be prescribed. The drug, a diuretic, has few side effects, and at high doses can clear oily skin and make unwanted hair finer. The combination of spironolactone and oral contraceptives is frequently used. If you are trying to conceive, however, do not take this drug because it can harm an unborn baby.

Bear in mind that it can take up to nine months to see effects on hair growth and a year to achieve peak effect. The hair will still be there, but will generally grow more slowly and will be lighter and finer. Electrolysis or repeated laser treatments are the only ways to get rid of the hair for extended periods or permanently.

A class of drugs called 5-alpha reductase inhibitors may help some women, though they should be taken only with extreme caution. These drugs inhibit an enzyme crucial to converting testosterone to dihydrotestosterone (DHT). Finasteride (Propecia and Proscar) and flutamide (Eulexin) are in this class. They were designed to treat prostate growth and cancer in men (which is exacerbated by excessive androgen levels), while Propecia is also prescribed as a treatment for male pattern baldness.

These drugs are not specifically approved by the U.S. Food and Drug Administration for use in women, and manufacturers advise against women taking them. If one is prescribed for you, you will have to be especially vigilant about birth control, because both cause birth defects. Flutamide has the potential, although infrequent, adverse effect of fatal liver toxicity.

Treating congenital adrenal hyperplasia (CAH) is a bit more complex, because CAH is characterized not just by high levels of androgens, but by low levels of two other hormones, cortisol and aldosterone. Treatment in an adult woman may incorporate a glucocorticoid, such as prednisone, to make up for the missing cortisol.

Androgen Deficiency

If you are androgen deficient, the benefits of a hormonal supplement can make it worth your while to investigate whether such a drug is right for you. Although not typically prescribed solely to prevent osteoporosis, testosterone supplements have been shown in several studies to not only slow bone loss, but also to stimulate bone formation in postmenopausal women and women with surgically induced menopause.

Some compounding pharmacies may be able to provide testosterone creams that are applied to the vulva for more targeted delivery of the hormone, but such formulations are not widely available. And there is a lack of published data demonstrating safety, whether or not they are effective and if the specially made batch will be exactly the same each time.

There's also a prescription combination estrogen (esterified estrogens) and testosterone (oral methyltestosterone) pill that may help combat androgen deficiency. These pills have never been formally approved by the FDA for such usages, and they may vary greatly by potency. There is conflicting evidence and opinion in the medical community concerning whether or not the benefits of the combination of estrogen and testosterone outweigh the risks, which may include increased risk of breast and endometrial cancer, adverse effects on blood cholesterol and liver toxicity.

Information from the Nurses' Health Study indicated that the combination of estrogen and androgen used to treat hypoandrogenism could increase breast cancer risk. However, other studies indicated androgens may decrease breast cancer risk. Follow-up studies on the Women's Health Initiative found women who received estrogen and no progestogen showed a significant decrease in cardiovascular disease (CVD) and breast cancer. This has caused a reconsideration of androgens added to estrogens. Still, the FDA requires demonstration of CVD and breast cancer safety for any product containing androgens or estrogen plus an androgen; that has not been done.

Women with androgen deficiency may benefit from treatment with dehydroepiandrosterone (DHEA), a hormone produced by the adrenal glands. DHEA is available over-the-counter without a prescription in the United States and is not FDA-regulated. It may improve such androgen-deficiency side effects as sexual dysfunction. However, while the hormone is available over the counter, it should not be taken without medical guidance.

The quantity and quality of DHEA contained in available preparations are not routinely monitored or tested for contaminants or consistency. Therefore, it's important that your health care professional monitor blood levels of DHEA, its metabolic products (estrogens and androgens) and any side effects if you're taking the hormone.

Since DHEA is converted to estrogen and testosterone in women, the levels of these hormones should also be measured when taking DHEA. The results of studies on the benefits of DHEA supplementation in both men and women with androgen deficiency have been mixed. A recent review of studies found no convincing evidence for the effectiveness of oral DHEA in treating symptoms of hypoandrogenism in women.

Androgen supplements are generally safe at the dosages prescribed for women, but possible side effects include facial hair growth, deepening of the voice, thinning hair and acne.

Noncosmetic side effects can include fluid retention, liver toxicity and unfavorable changes in your cholesterol levels, which should be monitored periodically. If they occur, side effects can be minimized or eliminated with lower androgen doses and can usually be reversed by discontinuing therapy. Higher doses can cause deepening of the voice or clitoral enlargement, which may be irreversible. However, this is not often seen in doses properly prescribed for women. Early side effects (those seen in the first 90 days of treatment) usually include oily skin or mild acne. These affects may be temporary and go away on their own. If they occur, talk to your health care professional about decreasing your dose before more serious side effects occur.

Research continues on testosterone patches, skin gels and vaginal suppositories or creams that could raise androgen levels in women. Testosterone patches for women, sold under the brand name Intrinsa, have been approved for use in Canada and Europe but not in the United States. These patches have recently been withdrawn from those markets for commercial reasons, not medical ones. A testosterone-containing skin gel, nasal spray and vaginal suppositories are in clinical trials or pending FDA approval. DHEA containing vaginal suppositories are also being investigated for vulvar and vaginal atrophy.

Androgen supplements are not the answer for everyone with a slumping libido and fatigue—particularly if you have any signs of androgen excess, such as hirsutism, acne or thinning hair. Such medications are also ruled out if you are pregnant or nursing.

As your body changes, it is very important to communicate with both your partner and your health care professional. Tell both about your symptoms and the changes in your body. Your partner's support can be helpful to ease the stress caused by symptoms that affect intimacy. Because every woman is unique, you and your health care professional will need to work together to determine which treatment option best meets your medical and personal needs.

Prevention

Researchers are still working to characterize fully the role of androgens in women and the nature of androgen disorders.

You can, however, prevent some of the worst consequences of androgen-related disorders. If you are hyperandrogenic, you may be at higher risk for glucose intolerance, diabetes and high cholesterol. Medication to reduce your androgen levels can reduce these risks, but you may want to talk to a health care professional about monitoring for these conditions and about lifestyle changes (such as diet and exercise) that might help reduce risk.

If you are hypoandrogenic, supplementing with testosterone may help prevent bone loss and osteoporosis and may provide a lift to your sex life and energy levels. Remember that communicating with your partner and health care professional about your symptoms is vital to maintaining a healthy lifestyle and sex life.

And be sure to tell your partner about the treatments recommended by your health care professional. Being open about problems and treatments is the best way to maintain a healthy relationship.

Facts to Know

1. Mistakenly thought of as only a male sex hormone, androgens are also natural to the female body, where they are produced in the ovaries, adrenal glands and other tissues.
2. Testosterone is the androgen you've probably already heard about. Others include dihydrotestosterone (DHT), androstenedione and dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S).
3. Androgens are partly responsible for the growth spurt at puberty and are believed to regulate the function of many organs, including the reproductive tract, bone, kidneys, liver and muscle.
4. Androgens have been reported to play a key role in a woman's sex drive, or libido, cognitive abilities, energy level and sense of well-being.
5. Androgens, either directly or indirectly through conversion to estrogen, affect bone cells or the environment surrounding bone cells, leading to better bone health.
6. Androgen production drops as you age. By the time you reach menopause, it has dropped 50 percent or more from its peak in your 20s.
7. The only time a sudden drop-off in androgen levels occurs is in women who have had their ovaries surgically removed (about half of all androgens are produced in a woman's adrenal glands and half in her ovaries).
8. If you take an androgen supplement, watch out for "virilizing" side effects, such as facial hair growth, thinning hair on your head and changes in your voice. If an androgen dose is too high, it can have adverse effects on your cholesterol levels.
9. The right oral contraceptive choice can reduce hyperandrogenic symptoms, while the wrong one can exacerbate them. The key component is the type of progestin included. Talk to your health care professional about a pill formulation whose progestin component is drospirenone, desogestrel or norgestimate.
10. If you have symptoms of hyperandrogenism (hirsutism, acne and/or irregular periods), see a health care professional. If the symptoms stem from polycystic ovary syndrome, you could be at higher risk for heart disease and diabetes.

Questions to Ask

Review the following Questions to Ask about androgen so you're prepared to discuss this important health issue with your health care professional.

1. Do you consider yourself up-to-date on hormonal disorders such as androgen deficiency and hyperandrogenism and their treatment? If not, can you make a referral to a health care professional with that expertise?
2. Do the symptoms I have suggest a possible androgenic disorder?
3. What other conditions could cause these symptoms?
4. Will an androgen abnormality affect my fertility?
5. How will you determine my androgen levels? What is too low? Too high?
6. I seem to have less interest in sex now that I'm older. What medical steps can be taken to address this issue?
7. Does the birth control pill I'm taking have anti-androgenic effects?
8. If medication is prescribed, what side effects should I watch for?
9. How long should I take this medication?
10. What happens if I stop taking the medication?

Key Q&A

Organizations and Support

For information and support on Androgen, please see the recommended organizations, books and Spanish-language resources listed below.

American College of Obstetricians and Gynecologists (ACOG)
Website: https://www.acog.org
Address: 409 12th Street, SW
P.O. Box 96920
Washington, DC 20090-6920
Phone: 202-638-5577
Email: resources@acog.org

Hormone Foundation
Website: https://www.hormone.org
Address: 8401 Connecticut Avenue, Suite 900
Chevy Chase, MD 20815
Hotline: 1-800-HORMONE (1-800-467-6663)
Email: hormone@endo-society.org

North American Menopause Society (NAMS)
Website: https://www.menopause.org/
Address: 30100 Chagrin Blvd, Suite 210
Pepper Pike, OH 44124
Email: info@menopause.org

Books

100 Questions & Answers About Menopause
by Ivy M. Alexander and Karla A. Knight

Dr. Susan Love's Menopause and Hormone Book
by Susan M. Love

It Hot In Here? Or Is It Me? The Complete Guide to Menopause
by Barbara Kantrowitz, Pat Wingert Kelly

Making Love the Way We Used to...or Better: Nine Secrets to Satisfying Midlife Sexuality
by Alan M. Altman, Laurie Ashner

Spanish-language resources

Medline Plus
US National Library of Medicine and the National Institutes of Health
Androgen Insensitivity Syndrome
Website: https://www.nlm.nih.gov/medlineplus/spanish/ency/article/001180.htm
Address: US National Library of Medicine
8601 Rockville Pike
Bethesda, MD 20894
Email: custserv@nlm.nih.gov