Hormonal Replacement Therapy - The Controversy
Postmenopausal Hormones and the Women's Health Initiative Study
Apr 27, 2009
Before menopause, women's ovaries produce the reproductive hormones, estrogen and progesterone.
During the years when women have constant production of estrogen, women benefit from the following estrogenic activities:
- protection against cardiovascular disease
- prevention against/reversal of bone degeneration (osteoporosis)
- reduction in sleep disorders
- protection against neurodegeneration
- reduction in susceptibility to urinary tract infections, urinary incontinence, and urinary urgency
During the years when women's ovaries are producing progesterone, women profit from the progestational activity of protection against neurodegeneration.
With all these protective effects, surely anyone would wish to continue the benefits by taking replacement hormones. However, the Women's Health Initiative study provided some troubling results.
The Women's Health Initiative Study
The Women's Health Initiative (WHI) study enrolled 16,808 healthy postmenopausal women and treated them daily with an estrogen, conjugated equine estrogen (CEE), plus medroxyprogesterone acetate (MPA), a synthetic progesterone, for 5.2 years. The study was stopped in July 2002 when the researchers discovered that the women taking CEE plus MPA demonstrated the following health problems in comparison to the women taking a placebo:
- a 41% increased risk of stroke
- a two-fold increased risk of venous thromboembolic events
- a 26% increased risk of invasive breast cancer
The study found that CEE plus MPA did confer the following health benefits:
- a 37% decrease in colorectal cancer
- a 31% decrease in hip fractures
However, because the overall risk of adverse health conditions was 15% greater than the benefit, the United States Department of Health and Human Services made the following recommendation: "The U. S. Preventative Task Force (USPTF) recommends against the routine use of estrogen and progestin for the prevention of chronic conditions in post-menopausal women."
Contradictory Studies
Two more recent studies indicate that the problems found in the WHI study may have been due to the synthetic progesterone used in the study, MPA, rather than due to hormone replacement itself.
- In December, 2003, a team at the University of South Florida published research (Thomas T, Rhodin J, Clark L, and Garces A., "Progestins initiate adverse events of menopausal estrogen therapy," Climacteric, 2003 Dec;6(4):293-301) demonstrating that the cardiovascular problems observed in the WHI study were reproducible with administration of MPA but not with administration of natural progesterone and not with the administration of CEE or another estrogen, 17-beta estradiol.
- A team at University Women's Hospital in Tuebingen, Germany published work in 2005 (Krämer EA, Seeger H, Krämer B, Wallwiener D, and Mueck AO, "The effects of progesterone, medroxyprogesterone acetate, and norethisterone on growth factor- and estradiol-treated human cancerous and noncancerous breast cells," Menopause, 2005 Jul-Aug; 12(4):468-74) demonstrating that MPA induced "the proliferation of benign or malignant human breast cells" but progesterone did not.
Is hormone replacement therapy with estrogen and natural progesterone beneficial? Is it safe? More studies are needed.
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