Although transdermal estradiol is clearly preferable to oral, conjugated equine estrogens, CEE the advantages of transdermal progesterone are less clear. A 2003 paper by Leonetti found that progesterone cream had an antiproliferative effect on an estrogen-stimulated endometrium, this is a positive finding but these results have not been confirmed by other researchers. Other researchers: Hermann and Nafziger compared progesterone exposure from an over-the-counter progesterone cream to oral micronized progesterone. They found no differences in the 24-hour progesterone exposure between progesterone cream and oral progesterone (as measured by the area-under-the curve from whole blood samples), indicating that whole blood progesterone levels from an over the counter progesterone cream are equivalent to those achieved from oral micronized progesterone. However, the Hermann study did not compare clinical effects for transdermal versus oral progesterone. From a patient preference perspective, progesterone cream is favored over oral micronized progesterone by 77% of patients.
In summary, current research indicates that oral administration of conjugated equine estrogens is associated with increased potential for harm compared to transdermal estradiol. Oral estrogens undergo first-pass metabolism by the liver, producing estrogen metabolites that may accumulate and increase the risk of coagulation and cancers. To date, there are no studies comparing the transdermal and oral forms of BiEst and TriEst.
Research supports the 3 common principles of bioidentical hormone replacement therapy, (BHRT):
- Use of bioidentical hormones
- Optimization of hormone deliver
- Use of physiologic doses
It appears that some bioidentical hormone options are safer than their non-bioidentical and synthetic analog counterparts. For example, it may be more breast-friendly to use estriol with estradiol, and there is evidence that progesterone is more breast-, heart-, and brain-friendly than synthetic progesterone analogs. In terms of the clinical efficacy of bioidentical hormones, Mahmud in his 2010 paper reported on the results of a bioidentical hormone protocol (including BiEst and progesterone) given to 189 women over a 12-month period. He found that 60% of women who had experienced menopausal weight gain lost weight on the bioidentical hormone protocol (average of 14.8 pounds) and 90% experienced improvement in mental symptoms. Mahmud reported that “complications described with traditional HRT did not develop in this population.
Despite these positive research findings, bioidentical hormones cannot be considered completely risk-free. All forms of hormone replacement should be considered to have the potential to increase the risk of hormone-related disorders. Therefore, patient follow-up to monitor benefits or adverse effects is essential regardless of the type of hormone used. In addition, anyone prescribing hormones to postmenopausal women is well-advised to keep abreast of current hormone research.
L’hermite M, Simoncini T, Fuller S, Genazzani AR. Could transdermal estradiol + progesterone be a safer postmenopausal HRT? A review. Maturitas. 2008;60:185-201. Wren B. Transdermal progesterone creams for postmenopausal women: more hype than hope? Med J Aust. 2005;182(5):237-238.Leonetti HB, Wilson KJ, Anasti JN. Topical progesterone cream has an anti-proliferative effect on estrogen-stimulated endometrium. Fertil Steril. 2003;79(1):221-222.Leonetti HB, Wilson KJ, Anasti JN. Topical progesterone cream has an anti-proliferative effect on estrogen-stimulated endometrium. Fertil Steril. 2003;79(1):221-222.Hermann AC, Nafziger AN, Victory J, Kulawy R, Rocci ML Jr, Bertino JS Jr. Over-the-counter progesterone cream produces significant drug exposure compared to a Food and Drug Administration-approved oral progesterone product. J Clin Pharmacol. 2005;45:614-619