Is Testosterone the Answer to Low Libido?

Researcher Susan Davis tells when and how it works

An Interview with Susan Davis, MBBS, FRACP, PhD

October, 2004

Contrary to popular belief, testosterone is not the exclusive property of men. Though it's called an "androgen" (from the Greek "andros," meaning man), women produce testosterone in their ovaries and elsewhere in the body from the hormones DHEA and DHEAS, which are created in the adrenal gland.

Though women have substantially less testosterone than men, it nevertheless powers up their sex drive and enhances mood and quality of life," says researcher Susan Davis, MBBS, PhD, director of Australia's National Health and Medical Research Council Center for the Study of Women's Health at Monash University in Melbourne, Australia. (http://www.health.gov.au/nhmrc/index.htm)

In recent years, testosterone therapy has been used to help women regain sexual function after surgical removal of the ovaries.¹ It may also be prescribed for women experiencing hormonal shifts as a result of chemotherapy or radiation.

Studies also show that testosterone helps women by boosting desire, energy, and mood and may also improve muscle tone.^2,3 In the United States, testosterone is generally given in combination with estrogen.

But testosterone therapy isn't always the cure for lagging libido, cautions Dr. Davis. It won't compensate for a failing relationship or alleviate mood swings or depression that stem from other causes.

Further, not all menopausal women complain of a fading sex drive. One large population-based study shows that the overall quality of a woman's relationship with her partner is the most important predictor of sexual satisfaction.⁴ Many women report a new interest in sex at this stage of life. Pregnancy is no longer a worry, and once children have left the nest, couples have time to get to know each other once again. Single women in new relationships also report high levels of sexual satisfaction during this time of life.

Nonetheless, says Dr. Davis, a woman's quality of life can plummet in tandem with declining testosterone levels.⁵ As Donna, a patient in her late 50s, said, "I don't care about sex any more. I used to like it, but it seems that my appetite is gone. When I do have sex, my orgasm is not the same. My husband and I both miss the kind of intimacy we had in 20 years of marriage. How can I get my desire back?"

As a practicing clinician, Dr. Davis wanted to help women like Donna. So, with other international experts on women's health, she began to ask, "What patients are most likely to benefit from testosterone replacement?"

In the last 10 years, Dr. Davis has directed major studies of testosterone therapy both in women undergoing natural menopause and those who have had their uterus and ovaries removed. Her work has contributed to our understanding of a condition called Androgen Deficiency Syndrome.⁶ Dr. Davis recently talked with our managing editor, Valerie Andrews, about her findings.

To echo your own question, who is most likely to benefit from testosterone treatment?

Testosterone therapy may be beneficial for women experiencing early ovarian failure, those who have had their ovaries surgically removed, and those suffering hormonal shifts in the wake of chemotherapy or radiation.

Women may also suffer from testosterone deficiency in the late reproductive years and after natural menopause.

Can you describe when and how testosterone and other hormones begin to wane?

Women normally have three major sex hormones circulating in their blood: estrogen, testosterone, and progesterone. Each is produced by the ovaries. Estrogen is also made throughout the body but particularly in body fat.

Testosterone can also be made in other parts of the body from hormones (DHEA and DHEAS) that are produced by the adrenal glands.

At menopause, estrogen and progesterone levels begin to shift, and we see the results in hot flashes and night sweats.

Testosterone drops most dramatically before menopause sets in. A woman in her 40s has on average only half of the testosterone and DHEAS circulating in her bloodstream that she had in her 20s. These hormones then continue to decrease very gradually over time.⁷ From their 30s onward, women may start feeling the effects of this.

Because symptoms related to testosterone insufficiency develop gradually, they often go undetected.

An exception to this is women who undergo surgical menopause. After the uterus and ovaries are removed, testosterone levels fall precipitously.⁸

If a woman in her 50s complains of low libido, is it always traceable to testosterone?

No. In a large random sample, we could not demonstrate a relationship between low testosterone and low libido.

In this study, low libido may have been caused by concurrent conditions such as thyroid disease, etc., relationship problems, stress, unrelated mood disorders, or by SSRI antidepressants or other medications.

We have to remember that multiple factors affect sexuality. While hormones like estrogen and testosterone play an important role, there is much to learn about behavioral and environmental factors that dampen desire.

Do standard blood tests indicate whether a woman has low testosterone and is "androgen deficient"?

We don't fully understand the relationship between testosterone levels and libido.

We can measure the amount of testosterone that available in the blood. But our research indicates that this is not indicative of who will benefit from testosterone therapy. So the main reason we measure testosterone is to identify women who should not be treated because their levels are already high enough.

Clinicians need to be aware that most methods for measuring testosterone are fairly imprecise and should not be used as a basis for diagnosing testosterone deficiency. They become even more difficult to interpret when blood levels of testosterone are low, such as after menopause or removal of the uterus and ovaries.

In general, blood levels are useful for comparison, for tracking the patient's response to therapy, or for determining whether she falls within what we consider "normal range."

One further caveat: As testosterone circulates in blood, most of it is bound to a protein called sex hormone binding globulin (SHBG), so clinicians should also measure SHBG levels to assist with diagnosis and management.⁹

Women who are taking estrogen in tablet form commonly have very high SHBG levels, and this limits the fraction of testosterone that circulates in the blood.^10-13

With these cautions in mind, are there any set guidelines for determining androgen deficiency?

At present this remains an area of uncertainty. It has been proposed that a testosterone level in the lowest 25 percent of what is considered "normal range" might indicate testosterone insufficiency. Yet this guideline was based on expert opinion, not on clinical studies. We also know that such an arbitrary cutoff does not determine who will benefit from testosterone therapy.¹⁴

Then how do you diagnose a testosterone deficiency?

By taking a thorough history. If estrogen levels are normal, a testosterone insufficiency can show up as low libido, decreased sexual receptivity and pleasure, low energy or persistent and unexplained fatigue, a depressed or dysphoric mood, a sense of diminished psychological well-being, and blunted motivation.

Clinicians should also check for decreased bone density, decreased muscle mass and strength, a redistribution of body fat, decreased sexual hair, and changes in cognition or memory.

If a woman complains of low libido, accompanied by depression or fatigue, the clinician must be sure to rule out other causes, such an iron deficiency, thyroid problems, mood disorders that stem from other sources, and other illnesses.

Some clinicians feel that hormone replacement therapy and the pill reduce a woman's testosterone levels and thereby affect desire. What is your view of this?

There are many reasons why the pill may impact libido. On a natural cycle, a woman's estrogen and testosterone levels fluctuate. Higher levels are related to increased desire. Some women are more easily aroused around the time of ovulation, when both testosterone and estrogen peak.^15-17

Hormone therapy (HT) and birth control pills create a steady state and keep a woman's hormones at the same level throughout her cycle, eliminating these peaks. Some researchers believe this may affect her patterns of arousal.

More importantly, oral HT and birth control pills increase the production of sex hormone binding globulin (SHBG).^18-21

As a result, more testosterone is tied up and there is less available to affect receptors in the brain. This reduction in bioavailable testosterone may play a role in the reduction in libido.

Still, not all women experience a decline in desire while taking HT or the pill. We don't need a warning label saying, "Caution. This treatments can affect libido." That would be a very dangerous message.

For some women HT and the pill may enhance sexual function. The birth control pill may alleviate heavy or continuous bleeding, reduce pain, and remove the fear of unwanted pregnancy. HT may alleviate hot flashes, improve mood, and also improve sexual response.^22-25

What are the side effects of testosterone therapy?

Women with very low levels of SHBG may suffer more side effects, and so testosterone therapy should be administered very cautiously and with careful monitoring in these patients.

Testosterone should also not be used by women who are pregnant or breast feeding or who have a suspected cancer. Some studies have shown that high levels of testosterone are more common in women who develop breast cancer. However, there is no data to indicate a causal link.

Finally, testosterone should not be given to women with severe acne or an unusual excess of body hair or thin scalp hair.

Are there any other concerns?

Any woman using testosterone during childbearing years must have reliable contraception. The reason for this is that testosterone may result in virilization of a female fetus if taken after conception.

No woman should continue testosterone treatment of any kind beyond six months if a clear benefit has not been achieved. And blood levels should be checked for any adverse changes in cholesterol.

Finally, there is no information regarding the safety of the use of testosterone in women long term, and patients should be apprised of this.

How many ways can testosterone be administered?

There are several modes of delivery. The mainstay in Australia is the testosterone implant, a pellet that's inserted underneath the fatty tissue in the abdomen, but that's not available in the U.S.

American woman are generally given testosterone in combination with estrogen, in a formula called Estratest®.

Estratest® is a combination of synthetic conjugated equine estrogens and methyl testosterone in pill form. It has approved by the FDA for the treatment of hot flashes and is now being prescribed off-label (for uses not approved by the FDA) for libido.

Methyl testosterone appears to reduce SHBG and increase the amount of bioavailable estrogen and testosterone. A number of studies have shown the benefits of this.²⁶

However, if the dose is too high, SHBG will dip, and a woman's testosterone will be too high.

An American pharmaceutical company (Proctor & Gamble) has also developed a testosterone patch for women.²⁷ It's in the final phases of clinical testing, but it isn't on the market yet.

While testosterone injections have been used in the past, these are only available in doses designed for men, and they result in very high levels that are more likely to cause side effects.

Finally, studies are under way evaluating the safety and effectiveness of a testosterone gel (Cellergy®) and a skin spray in women (Vivus®).

Testosterone creams or gels can be applied to the vaginal tissues.

Because individuals have varying rates of absorption, clinicians should compare testosterone readings on all patients after three weeks of treatment, and then review again at six to eight weeks.

How long can a woman take testosterone?

We have no data to answer that, but let me tell you more about Donna, who came to me in 1998 with low libido and fatigue. Donna met all the criteria for testosterone deficiency, and she has been on testosterone therapy for more than six years with no side effects. She is aware that we have no long-term studies on this treatment, and she has decided to keep on taking it. She told me, "I'd rather take the risk just to have these years feeling fully alive and to feel like myself again."

What are warning signs that a woman may be taking too much?

If the dose of the testosterone is in excess of a woman's needs, she may experience masculinization - a deepening of her voice, an excess of facial or body hair, and some scalp hair loss. High doses can also result in acne, fluid retention, enlargement of the clitoris, and adverse effects on blood cholesterol. These are rarely encountered if the appropriate dose is given, and a woman's blood levels are regularly monitored.

Blood levels achieved with therapy should be kept within the normal range for women.

In your most recent study, you found a new marker of low libido besides testosterone.

This was a surprise. When we looked at 1,423 women between the ages of 18 and 75, we found no relationship between low testosterone and low libido in women. Instead, we found that women under 45 who complained of low libido were more than three to four times more likely to have low levels of DHEA-sulphate (DHEAS).

This doesn't mean such women should be treated with DHEA. Instead, it suggests that DHEAS is a marker of low sex hormones overall, and this may turn out to be useful for diagnosis.

How would you help the woman having libido problems at midlife?

First, I'd try to determine the source of her difficulty. Does the problem stem from situational stress or from tension within her relationship or from depression or mood swings independent of her sexual problems?²⁸ If so, she might deal with this through counseling or medication.

Next, I'd check for hormonal deficiency. Is the woman receiving enough estrogen, either locally or systemically? If her estrogen is in normal range, then I would consider replacing testosterone.

I would measure blood levels of her testosterone - free and total - along with her sex hormone binding globulin to see if she falls in the normal-to-high range. If so, I'd keep on looking for other factors that could be causing a decline in desire.

Lastly, even with hormone replacement and additional testosterone, I would suggest that a woman and her partner may need to renew their sense of romance to fully regain their sexual intimacy.

Notes

Shifren, 2000
Alexander, 2004
Davis, 2002
Dennerstein, 2002
Zumoff, 1995
Fertility Sterility Supplement on Androgen Deficiency, Vol 77, No 4, Suppl 4, April 2002
Zumoff, 1995
Longcope,1990
Pugeat, 1996
Casson, 1997
Stomati, 1996
Nachtigall, 2000
Simon, 1999
Bachmann, 2002
Wilcox, 2004
Pillsworth, 2004
Bullivant, 2004
Casson, 1997
Stomati, 1996
Nachtigall, 2000
Simon, 1999
Sarrel, 2000
Sarrel, 1990
Sarrel, 1985
Levine, 1987
Lobo, 2003
Shifren, 2000
Alexander, 2003

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This article is for educational purposes only and is not intended as a substitute for medical advice. Please consult with a clinician to review any current symptoms and address your medical concerns.