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Endometrial Cancer: The Unopposed Estrogen Hypothesis

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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.

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We value and respect our HERWriters' experiences, but everyone is different. Many of our writers are speaking from personal experience, and what's worked for them may not work for you. Their articles are not a substitute for medical advice, although we hope you can gain knowledge from their insight.

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