Hormone Replacement Therapy for Women

For the over the past twenty five years, the medical community has been prescribing hormone replacement for women in menopause to protect against osteoporosis, heart disease, dementia and vaginal atrophy. Approximately 38% of postmenopausal women were using hormone replacement in 1995. Estrogen was the miracle drug that was going to keep us younger and healthier and prevent us from aging. It was known as the youth hormone. Despite the fact that many women had concerns about risks and side effects from HRT, the benefit was thought to out way the potential benefits. When the results of the Women’s Health Initiative study were released on July 9, 2002, it sent shock waves through the medical community and the millions of women taking hormones. The study reported that in the women taking estrogen plus progestin, there was an increase in breast cancer, stroke, and blood clots compare to placebo. The study was discontinued after 5.2 years as a result of these findings.
Many women under their doctor’s recommendation stopped taking HRT immediately and suffered from terrible withdrawal symptoms. Some women continued therapy but decided upon lower dosages or they switched to bio-identical hormones. Now the FDA has decided to put a black box warning label on any estrogen products. All of these concerns make it difficult to know what the best choices are for women, which estrogen to take and for how long.
The most important issue to explore is that any decision about hormone replacement, from whether or not to begin therapy to the form it takes must be decided on an individual basis for each woman based on her own family history, life style and personal risk factors. Each patient needs to work with her physician to decide what is best for her based on her biochemical individuality.
Physicians are trying to do the best for their patients to protect them from serious illnesses and help maintain quality of life. Since estrogen can help protect against certain illnesses and at the same time can increase the risk of others, it is often a difficult decision about whether or not to continue hormone replacement. We also do not have adequate research on all the different forms of hormone replacement to predict the long-term consequences of using HRT. Many studies group estrogen therapies together and yet there are differences between the different forms of hormones.
First, let us look at the Women’s Health Initiative research study itself. This study only involved two of the many different forms of estrogen available to women, Premarin and Prempro. These estrogens are conjugated estrogens from pregnant mare urine. In the study there were 38 cases of invasive breast cancer per 10,000 women in the group taking Prem-pro, the combination of estrogen and progesterone. The control group had 30 cases per 10,000 women. With eight more cases compared to control, the rate of increase was 26%, which is significant. A separate continued study to look at the risk of cardiovascular disease in women who have had a hysterectomy with Premarin only. Those results are discussed later.
The other important outcome of the first study was that there was an increased risk of stroke and formation of blood clots causing pulmonary embolism. There was a 42% drop out rate with women discontinuing the hormones due to side effects. Another difficulty was that 3444 women had vaginal bleeding. 248 of these women required a hysterectomy compared with 183 in the control group. On a positive side there were five fewer fractures per 10.000 and six fewer colorectal cancers. There was no statistical analysis on Alzheimer’s disease or dementia.
This study was limited to only these forms of hormones and only with one dosage. The authors reported in the comment section that the results do not necessarily apply to lower dosages of estrogen or other forms of hormone replacement. This raises a number of questions, especially since the group that had an increase in breast cancer used the synthetic progesterone in the Prem-pro. The progesterone used in the study, medroxyprogesterone has been known to have many side effects. In fact, many women have not tolerated the side effects from medroxyprogesterone that include bloating, breast tenderness, headaches and depression. It is also not clear if other forms of progesterone, either other synthetics or natural progesterone have the same increased risk.
The conclusion from the study was that the overall risks of taking this combination HRT formula is greater that the benefits. If you have a concern about heart disease and stroke, there is no reason to take this type of HRT for prevention. This form of estrogen and progestin can increase the risk of invasive breast cancer and does not reduce the risk of heart disease.
The later study published in 2004 using the Premarin alone reported a 39% increase in strokes, 23% decrease in invasive breast cancer and a 39% lower incidence of hip fractures. In 2006 another JAMA publication reported that in the estrogen alone arm of the study after 7.1 years there was no increase in the occurrence of breast cancer.
The conclusion from this study and the North American Menopause Association is that hormone replacement is indicated for the treatment of menopausal symptoms that are severe enough to interfere with the quality of life. The primary indications are relief from hot flashes, night sweats, vaginal dryness and the prevention of postmenopausal. Other reasons that cause women to want to take HRT including cognitive decline and skin changes have not been studied on their own but many women improvement when taking hormones.
For women now who have concerns about using hormone replacement, it is important to keep several things mind. We are aware that there are other issues in our environment that increase the risk of cancer, not only breast but other cancers. When you look at a study like this it is hard to know what other factors played into the increase in cancer, heart disease and stroke since these illnesses generally have more than one causative factor. It is not clear whether or not each patient in the study was screened for life style issues, family history, etc. In addition, the women in the WHI study tended to have a higher BMI ( Body mass index) and were not having menopausal symptoms. Thus they may not have been candidates for HRT. For each individual patient there are many issues to keep in mind.
When making a decision for you, it is important, to weigh all the different factors and life style issues. We know that diet, lifestyle and family history play a major role in the development of cancer and heart disease. There are many other alternatives that are available to women for prevention of the symptoms of menopause and aging. Estrogen isn’t the only treatment. Some women will benefit from taking estrogen but perhaps have fewer complications when using lower dosages of the bio-identical hormones or using other hormones such as DHEA or testosterone.
Here are some of the ways to help with your decision. If you want to start HRT, review the risks and benefits with your doctor. Consider your current state of health, your diet and medical risk factors as well as your symptoms.
If you are on HRT  feel you need to stop discuss this with your doctor. If you decide to stop taking estrogen, it is best for the body to do it gradually, not just suddenly stop the pills, creams or patches. Stopping suddenly will usually cause a reoccurrence of the uncomfortable symptoms a woman was when they started HRT initially. If doses are reduced slowly, many women will find that they can use smaller doses or may not need to take hormones at all. For women who have been taking hormones for longer than five years, it may be time to see if lower dosages or stopping all together is an option.
It is important to look at the reasons you started HRT in the first place. Was it just to prevent symptoms or was there a more significant problem such as osteoporosis, loss of libido, hot flashes, sleep issues or cognitive decline? Are there any other alternatives such as plant-based hormones or using other hormones besides estrogen?
In my practice, I prescribe a variety of hormones including progesterone, testosterone, DHEA and pregnenolone when the levels are low. When using these other hormones in a “hormone cocktail” the overall dosage of estrogen can be lowered and many women feel better overall. In reality, for years the ovaries and the adrenal glands have produced these other hormones. After menopause, the ovaries stop the production of high levels of these hormones but the adrenal glands should be pitching in to pick up some of the levels from the waning ovaries. Unfortunately, most women by the time they reach menopause have exhausted their adrenal glands and the production of these hormones is often negligible. It is an easy blood test to have performed by your doctor. Measure the levels of these other hormones and see if they are low. DHEA and pregnenolone are available over the counter but it is always advisable to start with small dosages.
Vaginal dryness is one of the bigger problems to occur when women stop taking hormones or enter into menopause. The vaginal tissues can often become dry and even painful when estrogen levels fall. This can be helped using topical estrogen, DHEA or testosterone. The Estring is a small ring that sits in the vagina and releases very small amounts of estrogen. It is changed every three months. The amount of estrogen released into the blood stream is minimal and believed to be safe. Vagifem tablets are another low dose forms of estrogen that can help with vaginal dryness that do not release very much estrogen into the blood stream. Compounded creams can also be prescribed.
Many women are using natural progesterone creams in low dosages that are available over the counter. Most of these creams have between 25 – 30 mg of progesterone per dosage. These creams have been reported to reduce the risk of hot flashes and help with sleep. There is no data to suggest that natural progesterone has the same risk of cancer as the progestin in the study. Unfortunately, there is no information about the long-term safety effects of using natural progesterone. Many doctors including myself who use bio-identical hormones find that the natural micronized progesterone as Prometrium or from the compounded pharmacy is much better tolerated and has fewer side effects when compared to the synthetic progestin, the one used in the study.
I prefer to prescribe bio-identical hormones for my patients and have seen many women report that they felt more “ like themselves” compared to using other products.
In the end, whether or not to use hormone replacement therapy and in what form is a very personal decision. Each woman should look at her medical history, risk factors, family history and symptoms and decide how to approach the issue. Prevention of cancer, heart disease, Alzheimer’s disease and osteoporosis requires a lot more that just whether or not to take hormones. Lifestyle issues such as stress, diet, exercise and the use of various supplements can play a major role. These topics will be discussed in upcoming articles.
Menopause: The Journal of The North American Menopause Society,Vol 21, (10) 2014
JAMA 288; 7, Aug 8, 2002

JAMA 295(14)1647-1657 JAMA. 291(14):1701-1712. 2004 JAMA 288. (7) Aug 8 2002

Writing Group for the Women’s Health Initiative; Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women; JAMA 288,(3) 2002