Before synthetic and nonhuman hormones were in common use, there was no need for a term like bioidentical. For the purpose of this review, bioidentical hormones are defined as hormones identical in structure to human hormones. However, when physicians began prescribing hormones to postmenopausal women, manufacturing limitations like the poor bioavailability of oral progesterone meant that bioidentical hormones were not an option. The fact that synthetic hormone analogs and nonhuman hormones were patentable, relatively inexpensive to produce, effective, and seemingly very safe led to their acceptance as the standard for hormone supplementation.
Conjugated equine estrogens (CEE) became a popular treatment for menopause symptoms after the 1968 book Feminine Forever. Over time though, continuous use of unopposed estrogen led to an increased incidence of endometrial cancer. This resulted in the addition of synthetic progesterone analogs like medroxyprogesterone acetate (MPA) to suppress endometrial growth and oppose the effects of estrogen. MPA was and still is very effective at suppressing endometrial growth, but its interactions with progesterone receptors in heart and bone tissue of postmenopausal women went largely unnoticed. Although small clinical trials and in vitro studies indicated MPA was not equivalent to progesterone, it wasn’t until large clinical trials reported that the combination of CEE and MPA increased the risk of heart attack, stroke, and cancer in postmenopausal women that hormone replacement really went under the microscope.
While combined CEE and MPA was the reigning champion of hormone replacement, a few innovative thinkers suggested that bioidentical hormones might be safer and more effective than nonhuman or synthetic molecules. Most influential was the late John R. Lee, MD, who, in addition to advocating for bioidentical progesterone as the ideal progestogen, also coined the term estrogen dominance. Erratic estrogen production combined with higher average estrogen levels are recognized characteristics of perimenopause, producing a condition of functional estrogen excess now commonly called estrogen dominance in the complementary medicine community. Lee devoted his career to educating women and healthcare providers on the benefits of using progesterone cream to correct this imbalance during perimenopause and beyond.
Meanwhile another innovator, Jonathan Wright, MD, evaluated women’s options for estrogen replacement. After menses ceases and menopause begins, estrogen levels begin to decline. In a quest for safer estrogen options, Wright reviewed the breast cancer research done by Henry Lemon, MD, in the 1960s. Lemon studied estriol, the weakest of the three main endogenous estrogens, and discovered that women with breast cancer had significantly lower urinary estriol numbers than healthy controls. Lemon’s research got Wright thinking that combining estriol with estradiol might be protective against cancer. He put this idea into practice and created BiEst (bi-estrogen) and TriEst (tri-estrogen). BiEst and TriEst can be compounded into capsules, creams, gels, and troche (lozenge) forms—BiEst usually in an 80:20 estriol-to-estradiol ratio and TriEst in an 80:10:10 estriol-to-estradiol-to-estrone ratio. The use of BiEst and TriEst is common in complementary medicine, and in some circles it has become the de facto definition of bioidentical hormone replacement (BHRT).
Once BiEst and TriEst made inroads into hormone replacement regimens, the debate over the safest and most effective forms of hormone replacement began to heat up.
Bioidentical Hormone Replacement
The term bioidentical hormone replacement has been variously interpreted. Some suggest BHRT is the practice of individualizing hormone therapy (by compounding individualized hormone doses), but most correctly interpret it as the use of hormones that are structurally identical to endogenous hormones. Therefore, the core principle of BHRT is the use of bioidentical hormones. There are 3 principles that complementary medicine practitioners generally adhere to when prescribing bioidentical hormone replacement.
••Use hormones identical in structure to endogenous, (your own) hormones.
••Optimize delivery: non-oral delivery methods may be preferable for estrogens.
••Use doses that mimic physiologically normal levels.
To understand the theory and importance of these principles, an awareness of the research comparing the various hormone products is essential.
Rationale for the Use of Bioidentical Hormones
By definition, the term bioidentical means life-identical—that is, hormones identical to those found in life (in this case, human). Literally then, bioidentical hormone replacement includes all human-identical hormones, not just compounded hormone products like BiEst, TriEst, and progesterone. For example: oral micronized progesterone and 17-beta estradiol patches are considered bioidentical because they are structurally identical to human hormones. A discussion of the clinically relevant differences between bioidentical and non-bioidentical /synthetic hormones illustrates why use of bioidentical hormones may be considered more beneficial.