Hysterectomy is one of the most common surgical procedures in women. Not all of these cases involve cancer, but many involve abnormal growth of the endometrial tissue. The unopposed estrogen hypothesis is a proposed mechanism, explained by Dr. Stalo Karageorgi of the Harvard School of Public Health and Dr. Alfred Mueck of the Center for Women's Health in Tuebingen, Germany. Estrogen stimulates the growth of endometrial tissue, while progesterone limits this effect. Too much estrogen or too little progesterone can lead to excessive cell growth, genetic errors, and malignant transformation.
Postmenopausal hormone replacement therapy became popular in the 1970's, and was followed by a rise in endometrial cancer in the 1980's. These initial pills were estrogen only. The increased cancer risk is a factor of 2 to 10, depending on how many years the hormones are used. Progestins were added to most hormone replacement pills to reduce this risk.
Combined oral contraceptives contain both estrogen and progestin, but in lower doses than postmenopausal hormone replacement pills. For comparison, a low dose birth control pill is Lo Ovral, which contains 0.03 mg estrogen and 0.3 mg progestin. Prempro, a postmenopausal therapy, is available in three dosages, with the highest one containing 0.625 mg estrogens and 5 mg progestin.
Mueck reported that combined oral contraceptives reduce the risk of endometrial cancer, while Karageorgi reported that postmenopausal hormone replacement therapy increases the risk. Here are the numbers:
1. Combined oral contraceptives, 50 percent reduced risk. This was independent of the dosage and type of progestin. The protective effect persisted for 10 to 20 years after the contraceptives were discontinued.
2. Postmenopausal hormone replacement therapy containing both estrogen and progestins, slightly increased risk, which depends on the number of days per month that progestins are included.
3. Postmenopausal hormone replacement therapy containing estrogen only, increased risk, up to a factor of 10.
Women of normal weight (body mass index less than 25) were most susceptible to the increased risk of postmenopausal hormone replacement therapy. Obese women have higher levels of naturally occurring estrogen, so Karageorgi suggested that these women may be acclimated to high levels of estrogen or that additional estrogen beyond a certain threshold does not change the risk.
References:
1. Karageorgi S et al, “Reproductive factors and postmenopausal hormone use in relation to endometrial cancer risk in the Nurses' Health Study cohort 1976 – 2004”, Int J Cancer. 2010 January 1; 126(1): 208-16.
2. Mueck AO et al, “Hormonal contraception and risk of endometrial cancer: A systematic review”, Endocrine-Related Cancer 2010; 17: R263-71.
3. Lo Ovral ingredients:
http://www.drugs.com/pro/lo-ovral.html
4. Prempro ingredients:
http://www.rxlist.com/prempro-drug.htm
Linda Fugate is a scientist and writer in Austin, Texas. She has a Ph.D. in Physics and an M.S. in Macromolecular Science and Engineering. Her background includes academic and industrial research in materials science. She currently writes song lyrics and health articles.