Testosterone and DHEA

Women naturally produce small amounts of the male hormone testosterone.  The ovaries produce most of the testosterone, and the adrenal glands and fat tissue also produce a small amount.  If the ovaries are removed surgically, there will be a major drop in testosterone levels. Menopause also causes testosterone levels to decrease.

 

The majority of testosterone is bound by a plasma protein, SHBG (serum hormone-binding globulin), and only the small amount that is " free" is active in the body. SHBG also binds estrogen but has much more of an affinity for testosterone.  Paradoxically, the estrogen that women use in HRT for positive benefits has the effect of increasing SHBG, resulting in even lower testosterone levels.

 

Effects of Testosterone

Low levels of testosterone in women have been associated with sexual dysfunction, fatigue, loss of pubic hair, and decreased bone and muscle mass.  High levels of testosterone have been associated with "male" side effects such as acne, hair growth, and voice changes.  High doses will also have a negative effect on HDL ("good" cholesterol).  For this reason, it is very important that only small doses of this hormone be used in women.  The term often referred to is "physiologic doses"--just the amount to replace what your body naturally produced.

Bone Health: Testosterone may also have a positive effect on bone health, although there is much more research needed.  There have been a few studies demonstrating that estrogen and testosterone taken together have more of a positive effect on bone density than estrogen taken alone.

Libido: The use of testosterone to improve libido is the current hot topic on the afternoon talk-shows.  The loss of sexual desire in women can be due to a variety of factors.  Therefore, it would seem that testosterone therapy would be most appropriate for women who have an actual deficiency of the hormone.  It is doubtful that testosterone therapy would be useful when the loss of libido is caused by certain medications.  The antidepressants Prozac, Paxil, and Zoloft often cause a loss of libido due to their effect on serotonin, not on testosterone.

Treatment:  Women seem to have a variable response to testosterone therapy, possibly due to genetic differences in the amount of receptor sites and due to age-related diminished receptor sites.  Also, there appears to be a lag time of as long as several weeks before benefits occur.

Testosterone therapy does not seem to follow a normal dose response curve, where increasing the dose increases the benefits.  Research has shown that increasing testosterone to above normal levels does not give a resulting increase in libido but will actually increase side effects.  High doses of testosterone will unnecessarily increase existing estrogen levels in those women taking hormone replacement therapy (HRT) because the body converts testosterone to estradiol.  Therefore, some primary care providers feel that women on testosterone therapy can use lower doses of estrogen.

At the moment, there are not a lot of studies regarding testosterone therapy for women. Some primary care providers will take a blood sample and test for "free" testosterone; others feel that blood testing may not be necessary and may give a small dose while monitoring the results over a few months.  It must be noted that many endocrine specialists do not feel that the "do-it-yourself salivary tests ", despite their popularity, are as accurate as blood tests.

Types of Therapy

Oral

Testosterone is often referred to as "natural "testosterone.  It is manufactured in the laboratory from soybeans; however, the ability of the final compound to be biologically identical to what the body naturally produces is the best description of natural.  In this sense, testosterone can be considered natural. 

The drawback of natural testosterone is that it is poorly absorbed in the stomach and rapidly inactivated by the liver.  Its oral uses are limited. Testosterone can be compounded in a lozenge, which allows for absorption and bypasses the liver effect. 

Methyltestosterone is the most widely used oral testosterone. It is a synthetic form of testosterone that was developed to circumvent the absorption problems of testosterone. However, unlike testosterone, it is not converted in the body to estradiol and may prove useful for women who want to limit their exposure to estrogen.

Methyltestosterone is combined with estrogen in the commercial products Estratest (2.5 mg) and Estratest Half Strength (1.25 mg).  Some researchers have suggested that the doses in even the half-strength product may be too high for many women, producing acne and hair growth.  The suggested doses are in the range of 0.25 mg – 0.75 mg, which are available as capsules a compounding pharmacy.

Topical

 At present, compounding pharmacies are the only source of topical testosterone formulations for women.   In Europe, studies are being done on a low dose testosterone transdermal patch, which is not available in the U.S. yet.  The commercial transdermal patches for men are too strong for female use.

 

Vaginal

Testosterone vaginal ointment has been used for years to treat a certain type of vaginal atrophy called lichens sclerosus.  However for this use, testosterone is only used daily until tissue health is restored; then it is only used once or twice a week. The long term  daily genital use of testosterone has been associated with unwanted side effects such as clitoral enlargement.  The most prescribed strength is Testosterone Ointment 2%.

 

Transdermal

The transdermal creams and gels are the most utilized formulations in testosterone therapy.  Special gels have been developed because the mineral oil and petrolatum in ointments tend to reduce the absorption of testosterone on intact skin.  One of the most popular gels is called organogel (or PLO gel), which is a water-based product mixed with special skin penetrating lipids.

 

Although the transdermal formulations can be applied anywhere, many primary care providers feel that they work best in an area where the skin is thin and there are less fat cells. For this reason, it is usually prescribed for application to the inside of the forearm or upper arm (at bedtime).  The organogel is not as easy to apply as some of the less effective creams, so doses of  ¼ teaspoonful or less should be used.  Larger amounts may leave a sticky residue.

Transdermal testosterone will bypass the liver effect and produce satisfactory blood levels.  It seems strange to some that as little as 1/8 teaspoonful of testosterone gel will work, but in an effective base (like organogel) this hormone is very well absorbed through the skin.   Many of you will remember the Brylcreem ad of the 1960’s--"a little dab will do you".  Keep this in mind with transdermal testosterone.  You should not exceed the dose prescribed by your primary care provider.  It is important that the doses be kept low to eliminate side effects.

Transdermal testosterone is compounded in a wide variety of strengths (0.25 % - 2.5 %). There are no major studies to indicate exactly what blood level postmenopausal women should have and what the daily dose should be.  Many primary care providers have found that a dose in the range of 2.5 mg – 5.0 mg has proved satisfactory for many women with testosterone deficiency.

 

DHEA

Fortunately we have acronyms in medicine. Can you imagine having to continually refer to "dehydroepiandrosterone" instead of DHEA?  In the past few years, an abundance of medical claims have been made about this substance--often referred to as a prohormone because it is converted into other hormones (in this case testosterone) in the body.

Benefits: There are few studies on testosterone therapy for women, and there are even fewer on DHEA.  Many of the benefits attributed to DHEA--anti-aging, disease reduction, and weight loss--were done on animals that don’t normally produce DHEA.  It is not known what the effects would be on humans, particularly females.

It appears that DHEA may have some effect on the brain and might possibly be used for depressed postmenopausal women.   However,  large scale studies of DHEA are needed before it becomes widely used for the treatment of depression.

DHEA is converted to testosterone in the body and may have a therapeutic role in raising testosterone levels in women.  Like testosterone, high doses can lead to side effects such as masculinization and the lowering of HDL ("good" cholesterol).  For this reason, primary care providers often use it in doses 25 mg or lower.

Availability: DHEA is available without a prescription as an over-the-counter (OTC) supplement, and many take it without medical supervision.  DHEA will have a significant effect on the levels of other hormones;  it is converted into testosterone and then the testosterone is converted into estrogen.  Guessing how much you need can lead to higher levels of hormones and a greater risk of side effects, so you should consult your primary care provider before you start using DHEA.

Quality control of non-prescription DHEA products can be a problem.  Due to the current unregulated status of supplements, you can't be assured that non-prescription DHEA contains the labeled, or even any, amount of DHEA.  Several studies have shown this to be the case with many other expensive supplements.

Compounded DHEA: Non-prescription tablets usually use relatively inexpensive plain DHEA;  compounding pharmacies formulate micronized (superfine particles) DHEA, often in an oil suspension, to make capsules that are much better absorbed.  Like natural progesterone in oil capsules,  compounded DHEA capsules go directly into the lymph system and bypass much of the liver.

Compounding pharmacies also make a DHEA  transdermal gel in much the same manner as the testosterone gel is formulated.  This gel form bypasses the liver and allows the DHEA to be converted to testosterone and estrogen in peripheral tissues at a much slower rate.  This may prove to be the most appropriate way of administering DHEA.

The DHEA products formulated in a compounding pharmacy are only available on prescription because of their potency.  Doses of these products should probably not exceed 25 mg daily.