Current Drug Therapy

Bioidentical hormone therapy: Clarifying the misconceptions

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References

Progestogens can also be given by different routes

Oral progesterone has poor gastrointestinal absorption and a short half-life.10 Therefore, it is micronized with oil for better absorption. Reported side effects include sedative and anesthetic effects; therefore, it is recommended that oral progesterone be taken at bedtime.9 Medroxyprogesterone acetate may interfere more with estrogen’s positive effects on cholesterol than micronized progesterone does.13

Topical progesterone preparations vary widely in dosage and formulation. Over-the-counter progesterone creams vary in concentration from no active ingredient to 450 mg or more of progesterone per ounce. Application sites for progesterone cream include the inner arm, chest, and inner thigh. No transdermal hormone should be applied to areas of the body that may allow possible contact and transference to others.

Progestogen products

Progestogen products include “natural” progesterone and synthetic progestins. They should be given concurrently with estrogen therapy in women who have an intact uterus to prevent endometrial hyperplasia.9

Bioidentical progesterone is micronized in the laboratory for better absorption in the gut.2

Nonbioidentical progestins significantly differ from endogenous progesterone in both their molecular structure and function.10 Progestins include oral medroxyprogesterone acetate, norethindrone acetate, drospirenone, and levonorgestrel (Table 3).

Misconception: Transdermal progesterone protects the endometrium

In general, transdermal progesterone should be avoided, as it does not protect against endometrial cancer.

Many forms of progesterone are available by prescription at compounding pharmacies as lotions, gels, creams, capsules, trochees, and suppositories.9 Transdermal progesterone creams are also available over the counter at health stores. Some of these creams contain only diosgenin, a progesterone precursor derived from wild yams.10 Diosgenin cannot be converted into progesterone within the body and thus does not provide an adequate amount of absorbable progesterone.9 Therefore, progesterone cream that contains only diosgenin is not effective in preventing endometrial hyperplasia and cancer.

To achieve a physiologic response, progesterone levels must be at least in the nanogram range.10 Transdermal progesterone cream has not been shown to reach this level and may not significantly improve vasomotor symptoms.12 Some practitioners prescribe cream that contains more than 400 mg progesterone per ounce. This may achieve physiologic levels of progesterone, but no improvement has been proven for bone mineral density or endometrial protection. In general, no transdermal progesterone cream can be assumed to protect the endometrium against the stimulatory effects of estrogen.

CUSTOM COMPOUNDING AND SALIVA TESTING TO INDIVIDUALIZE THERAPY

Some clinicians who prescribe compounded hormones order saliva tests. They argue the tests help them to establish which hormones are deficient and therefore to customize therapy.12 The basis for this is that saliva is similar to an ultrafiltrate of blood and, theoretically, hormone levels in saliva should represent the bioavailable hormone in serum.10

Unfortunately, this testing is often unreliable due to poor stability of samples in storage and large interassay variability.10 Many factors may alter hormone levels in saliva and make test results unreproducible, including the time of day the sample is collected and dietary habits.10 The FDA states that there is no scientific basis for using salivary testing to adjust hormone levels.2

Levels of drugs with clearance that varies depending on hepatic enzyme activity and plasma binding (capacity-limited metabolism) such as estradiol and testosterone can be monitored with total blood serum concentrations.10 However, many physiologic effects of estrogens are determined intracellularly at the level of tissues.10 Therefore, although levels during therapy with bioidentical estrogens can be monitored more precisely, the FDA states that hormone therapy should be guided by symptom response and findings on physical examination and not by hormone levels alone.2,12 It may be reasonable to order serum levels of estradiol in women being treated with therapeutic doses of bioidentical estrogen but still not achieving symptom relief. If women are being treated with conjugated equine estrogens, serum levels cannot be monitored. Total estrogen can be monitored as a send-out laboratory test.

MISCONCEPTION: HORMONE THERAPY IS A FOUNTAIN OF YOUTH

Customized compounded hormonal therapy is marketed as being able to help with rejuvenation, improve memory, sexual function, and reverse the aging process, essentially promising to be an elixir or fountain of youth.

These claims are not substantiated. However, the actual benefits of hormone therapy in women who have menopausal symptoms include alleviation of moderate to severe vasomotor symptoms and vaginal atrophy that can result in dyspareunia. By alleviating their symptoms, hormone therapy improves women’s quality of life. It also reduces the incidence of postmenopausal osteoporotic fractures.

A research finding that is often overlooked is that postmenopausal women younger than 60 years who started estrogen or estrogenprogestin therapy soon after menopause had a 30% lower rate of death from all causes.2,14 This difference was statistically significant when the estrogen and estrogen-progestin therapy groups were combined. No reduction in the mortality rate was seen if therapy was started after age 60.

MISCONCEPTION: COMPOUNDED THERAPY IS SAFER

Compounded hormone therapy is often marketed as a safer or more effective alternative to government-regulated and approved therapy. Unfortunately, these claims are often false and misleading, and safety information is not consistently provided to patients as is required with FDA-regulated hormone therapy.2

Since these compounds have not been approved by the FDA, there is no guarantee that the ingredients have been tested for purity, potency, and efficacy. There is no batch standardization. These unregulated therapies may use unapproved ingredients, routes of administration, and mixtures with contaminants such as dyes and preservatives.2

Also, custom-compounded prescriptions are considered experimental. Therefore, they are often not covered by insurance, and many women must pay for them out of pocket.11

The North American Menopause Society does not recommend custom-mixed products over well-tested, government-approved commercial products for most women.2 All bioidentical hormone prescriptions should include a patient package insert,11 identical to that required of FDA-approved products.2

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