All the adverse effects from the oral route of administration of estrogen as previously outlined in Outliving Your Ovaries can also occur from oral Prempro. However, the addition of the progestin seems to confer additional cardiac risk. Perhaps giving progestins daily instead of in cycles of 14 days each calendar month may be a factor in this increased risk. Earlier observational studies, like the Nurses’ Health Study, predominantly used oral cyclic progestins and did not show an increased risk of heart disease.
While estrogen increases the beneficial HDL cholesterol, adding a continuous synthetic oral progestin lowers HDL by 8 to 18%. Addition of oral, micronized progesterone causes little or no adverse effects on HDL. An animal study showed that adding MPA to estradiol blocks the conversion of estradiol to an important beneficial byproduct made in the liver called 2-methoxyestradiol.
In the Women’s Health Initiative, a randomized, placebo-controlled trial showed no change in the incidence of heart disease in women starting Prempro within 10 years of menopause when compared with placebo. Women starting Prempro 10 years after menopause had an increased risk of heart disease which increased the more time had elapsed since menopause.
The 2009 Danish Study, an observational study of 698,098 women, found those who took continuous combined oral HRT had a 35% increased risk of heart attacks compared to women who did not take hormones. In the women taking topical estradiol plus cyclic progesterone or cyclic progestin, there were 38% fewer heart attacks.
I had an acquaintance, Janet, who became newly menopausal and was exhibiting the typical symptoms. Her physician promptly started her on a daily combination pill containing synthetic estrogen and progestin. Within days of starting that therapy, she developed new onset chest pain sending her to the emergency room (ER). At the ER, Janet was evaluated and sent home and referred to a cardiologist who did stress testing and told her everything was normal. When she continued to have intermittent chest pain, her physician changed her to a combined topical estradiol/synthetic progestin patch. The pain lessened but she still had occasional chest pain. Not until she was finally put on topical estradiol with cyclic oral progesterone did she finally have resolution of her chest discomfort. Imagine the cost savings and the angst that would have been avoided if she had just been put on topical estradiol and cyclic progesterone from the beginning!
Excerpt from “Outliving Your Ovaries” © 2012 by Marina Johnson MD. Dr. Johnson has no financial conflicts of interest or ties to any pharmaceutical company. Her only objective is determining the most effective, safest therapy for patients.