The Women's Journal

The Truth About Unopposed Estrogen

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By Brian J. Shiple, D.O. & Kelly P. Shiple, PA-C


Bioidentical hormones have earned a negative and controversial reputation thanks to the female hormones estrogen and progesterone. One of the most common questions we get from patients interested in hormone replacement is, “Do estrogen and progesterone cause cancer?” The short answer is no, not necessarily. The long answer is the reason for this article.

Bioidentical hormone replacement therapy (BHRT) involves prescribing biologically identical hormones to those that are made by the body. This type of hormone replacement is generally safe, as the body’s receptor sites recognize these supplements and medications as the same as the body’s own hormones. When synthetic hormones are used, the body sees them as foreign, resulting in many risks, complications, and side effects that are not seen with bioidentical hormones.

The controversy over prescribing estrogen and progesterone began when the results of the Women’s Health Initiative (WHI) trial were published in 2002. The WHI trial was one of the largest prevention studies conducted to observe and address different health problems causing mortality in postmenopausal women. Participants were split into several different groups, including a synthetic estrogen group using Premarin only, a combination group using a synthetic “progesterone-like” progestin with synthetic estrogen in a drug called Prempro, and a placebo group. It was found that Prempro increased the risk of breast cancer and heart disease in menopausal women, while these risks were actually reduced in the Premarin only group. The incorrect conclusion was drawn that estrogen is harmful, when it was actually the progestin that increased these risks. This conclusion was extrapolated and it was recommended that everyone avoid all hormone replacement. Currently, the recommendation is to only use hormone replacement for menopausal symptoms at the lowest dose for the shortest period of time possible. This is true only in relation to synthetic hormones. Bioidentical hormones have been studied over the past 50 years and have not been linked to the same risks. Bioidentical estrogen (estradiol) has not been linked to an increase in heart disease or blood clots. Bioidentical progesterone (prometrium) can help decrease the risk of breast and uterine cancer. Both have been found to be beneficial and safe for postmenopausal women when prescribed together.

The most important of these two hormones is progesterone. Deficiencies in this hormone can affect women of all ages at all stages of life. Menopausal women who lack this hormone as well as premenopausal women whose progesterone levels begin to drop as they approach “the change” may experience menopausal symptoms such as hot flashes, night sweats, and mood swings. Young women who begin to experience signs and symptoms of a condition called polycystic ovarian syndrome (PCOS) suffer from severe premenstrual syndrome (PMS) to include anxiety, depression, and cramping during the two weeks prior to their period due to a deficiency in progesterone. Post-partum depression and high miscarriage rates have even been linked to a lack of progesterone. This is because the placenta creates its own progesterone source in order to support a successful pregnancy, but this does not start until the second trimester and ends when the placenta is delivered after birth. The increase in progesterone during pregnancy is the reason some women love being pregnant and can be more pleasant than usual during this time. Lastly, a common cause of chronic headaches and insomnia in women is actually a lack of progesterone, as well.

The benefits of progesterone don’t stop there. Progesterone has also been proven to help magnify the effects and benefits of estrogen. These include the prevention of osteoporosis and dementia, and protection against uterine and breast cancer. Estrogen should always be used in combination with progesterone. There are no exceptions. The reason for this is that estrogen causes cells to proliferate or multiply in the breasts and uterus. When abnormal cells are present in either area, the addition of higher levels of estrogen causes them to multiply and increases the risk for cancer. Progesterone is apoptotic to cancer cells in the breast and uterus, meaning it actually kills them. Many women are put on estrogen by itself after having a hysterectomy and are told they don’t need progesterone because they do not have a uterus. Not only are there so many great reasons to take progesterone, there are virtually no reasons not to and health risks are potentially increased by using estrogen without progesterone. Women who have not yet gone through menopause, by definition, a time of at least one year after the last menstrual period, should not be on estrogen due to the fact that estrogen is still being produced. Excess estrogen can cause estrogen dominance and worsen premenopausal symptoms.

Both estrogen and progesterone come in oral and transdermal cream forms. Estrogen can be prescribed orally or transdermally. Both forms increase blood levels of estrogen enough to provide benefit and offer protection. However, oral is much more beneficial than transdermal. Progesterone should only be prescribed and taken orally, as the transdermal form does not raise blood levels enough to offer protection and oppose estrogen. Any woman who is on oral or transdermal estrogen with transdermal progesterone is being exposed to unopposed estrogen, which may increase the risk for breast cancer, uterine cancer, heart disease, stroke, and blood clots.

Although BHRT may lower the risk of certain diseases it cannot completely eliminate risk. We cannot change family history, cure a disease process that is currently occurring in the body, or undo harmful environmental exposures. This makes keeping up with health maintenance exams extremely important so that any worrisome conditions may be discovered and treated as early as possible. Self-breast exams, mammograms, pap smears, and regular gynecology visits are necessary to keep up with the standard of care.

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