Your Health After Hormone Replacement Therapy (HRT)

Recent news reports have highlighted the findings of the Womens Health Initiative Study, the Million Womens Study, and the Nurses Health Study which revealed potential risks involved in hormone replacement therapy (HRT), resulting in a great deal of confusion. As a result of these studies, the rate of HRT discontinuation increased from 2.5% to 13.8% (1). This article will discuss the details surrounding these studies as well as their interpretation or misinterpretation by the media.

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During menopause, estrogen levels drop, leading to the onset of menopausal symptoms such as hot flashes, night sweats, vaginal dryness, and bone loss. Replacing the lost estrogen using HRT has been a traditional therapy used to alleviate the symptoms associated with menopause.

The Womens Health Initiative study concerning the effect of HRT on heart disease, stroke, breast cancer, and colorectal cancer and bone fractures was conducted in 1993-1998 and included more than 27,000 women and 40 clinical centers in the U.S. (2, 3). The purpose of these trials was to determine if there we're benefits in taking HRT in older women, thereby preventing chronic disease.

Before these studies we're initiated, there was some evidence that HRT might give additional health benefits such as a reduction in a womans risk of heart disease. For example, women who ingested estrogen orally for relief from menopausal symptoms also had decreased LDL (bad cholesterol) levels as well as increased HDL (good cholesterol) levels after starting HRT (4). Furthermore, there was evidence that estrogen may prevent atherosclerosis (hardening of the arteries) (4). Consequently, the aim of the Womens Health Initiative was to determine if HRT could reduce a womans risk of heart disease.

Two large studies we're initiated at approximately the same time by the Womens Health Initiative. The first study was concerned with postmenopausal women who had an intact uterus (no hysterectomy) taking a combination of estrogen and progestin (2). The second study involved postmenopausal women with a hysterectomy taking estrogen alone (3). Both studies had two groups, one of which took the hormone and one that took a placebo. Each study will be considered separately in this article.

In 2002, the results from the estrogen and progestin study in women with an intact uterus we're published. Due to concerns pertaining to endometrial cancer (uterine cancer), women with an intact uterus primarily take a combination HRT, including estrogen and progestin instead of estrogen alone. The study was intended to last approximately 9 years, but was ended after 5.6 years due to increased risk of breast cancer and abnormal mammograms in the group of women taking the hormones (2, 5). Cases of invasive colorectal cancer we're reduced in women taking the hormones; however, the risks of developing breast cancer outweighed any benefits that we're observed.

Because the study was ended prematurely out of concern that the treatment was causing more damage than benefits, news spread fast that women on HRT would get breast cancer or heart disease. Was all the anxiety and worry warranted? A closer look at the actual numbers from the study show that out of 10,000 women on combined HRT, 8 more developed breast cancer, 8 more had strokes, 8 more had pulmonary emboli, 7 more had heart attacks, 6 fewer had colorectal cancer and 5 fewer had hip fractures compared to the women taking the placebo (2). So, while the HRT group did have more cases of breast cancer and heart disease, not every woman taking them was affected.

At this point, you may be wondering how HRT leads to an increased risk of heart disease when estrogen alone induces a favorable blood lipid profile (higher good cholesterol levels and lower bad cholesterol levels). The exact way in which HRT increases the chance of a women developing heart disease is not known. However, there is some evidence that progestin actually negates some of the positive influences of estrogen in a womans body. This may explain why women taking estrogen alone may have better blood lipid profiles after HRT, but women taking the combination HRT don't receive the benefits.

The Womens Health Initiatives Estrogen alone study in women with hysterectomys suffered a similar fate in that it was also ended prematurely (after approximately 7 years) due to increased incidences of stroke in the group of women on HRT (2). Furthermore, any benefit in heart disease was not seen. Interestingly, there was a possible reduction in one type of breast cancer risk (ductal carcinoma) in the women who took the estrogen although this reduction wasnt statistically significant. However, a more in depth analysis of the data detailing the breast cancer incidences showed that while there may be a reduction in breast cancer incidence, there we're more abnormal mammograms that required short interval follow-up in the women on HRT (6). In contrast, the Million Womens Study found that both estrogen alone and the combination estrogen and progestin increased a womans risk of developing breast cancer (7).

Subsequent studies have found that the type of hormones and how much you take may determine the type of breast cancer for which you are most at risk (8). There are about 9 different types of breast cancer which are determined by the area in which the tumor grows or the cell type that becomes the tumor. The cartoon shows the two most common types of breast cancer, ductal and lobular, and where they arise. Tubular carcinoma is a third major type of breast cancer that is similar to ductal carcinoma. These tumors are smaller in size and more difficult to detect by palpitation.

After analyzing over 5,000 women, researchers found that women who used medium potency estrogen alone (estradiol/ 2 mg orally/ day or 50 g transdermally/ day) for more than 5 years had increase risk of developing ductal and lobular carcinomas whereas women using a combination of estrogen and progestin (1 mg norethisterone acetate/ day, 250 g levonorgestrel/ day) for more than 5 years had an increased risk of developing all three major types of breast cancer, ductal, lobular and tubular (8). Finally, women who used low potency estrogen (1 mg/ day estriol) had an increased risk of developing lobular carcinoma. Importantly, in women who had a BMI greater than 27, the risk of developing ductal or lobular carcinoma was the same, whether or not they used the combination estrogen and progestin HRT, indicating that weight may influence a persons risk of developing breast cancer to a greater degree than HRT (8).

As with most scientific studies, interpreting what these studies mean for the average women about to go through menopause is not always so clear. Should they consider HRT, which type, for how long, and is it worth it are all valid questions especially after these studies?

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Posted in Dentistry Post Date 06/03/2018






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