by Marcelle Pick, OB/GYN NP
Several years have passed since researchers first published data from the Women’s Health Initiative (WHI) postmenopausal hormone therapy trials. As newer studies appeared and the WHI data were reanalyzed, headlines have continued to sensationalize the findings on the risks of HRT: first they clanged the alarm that HRT is dangerous to your health (as it can be in certain circumstances), then outright proclaimed “HRT fine for younger women,” (which, again, it can be). We were dismayed when the FDA and Big Pharma lay siege to compounded bioidentical hormones, then sighed with relief as we watched bioidentical HRT come of age.
What’s obscured by these mixed messages is that emerging research confirms the position we’ve held all along: a woman’s risk-to-benefit ratio when taking hormones is just as individual as she is. This is the news you can use.
But confusion abounds regarding the safety of HRT. How can a woman determine her personal risk and make an informed decision? This seems a good time to put some perspective on the findings that cause such concern and confusion among women — and their healthcare providers, too.
The risks and benefits of HRT are not cut-and-dried
We agree that women should consider alternatives to synthetic HRT, but much of the fear and confusion is needless. Let’s consider both sides of the debate, starting with the point of view that argues that the WHI findings show that all HRT is bad and no one should use it. Here are the concepts I’d like to share regarding this premise.
- Apples to oranges. First, the majority of studies published to date have concerned synthetic HRT, mostly Premarin and Prempro. The few that have looked at bioidentical hormones clearly demonstrate that synthetic HRT and bioidentical HRT are not the same. The leading case of mistaken identity would be synthetic progestins versus bioidentical progesterone — they have totally different effects in the body and should never be lumped together when quantifying risks and side effects.
- Timing is of the essence. Most of the women participating in the WHI studies began taking HRT approximately 12 years after menopause. Their bodies experienced a sharp increase in sex hormones long after the natural decline of sex hormone levels, in direct opposition to what Nature intended. So the 2002 WHI data probably doesn’t accurately reflect the health risks of HRT for women in their 40’s and 50’s, who are the typical hormone therapy users. Re-analysis of the data on women in their 50’s suggests a lower level of risk for this younger age category, which is just what we’d expect. So how do women know when to stop? Additional findings suggest the risks of hormones are minimized when taken for the shortest possible time. Current thinking is that most women should try to go off HRT after one to two years, but a longer period may be warranted in certain situations.
- Routes of delivery. This term applies to how the hormone therapy gets into your blood stream, and it has a significant impact on risk. Hormones delivered across the skin (transdermal), the tongue (sublingual, or “melt”), or via the genitals (transvaginal) are associated with lower risk profiles than pill forms, which have to pass through the digestive tract. The former routes of administration allow hormones to more directly enter your bloodstream and reach the cells of the target tissues, by-passing the digestive system and metabolic pathways of the liver, where many of the risk factors are thought to originate.
- Freedom to choose. We have found that HRT works beautifully for some women, and the benefits of HRT may outweigh its risks for women with severe symptoms, premature ovarian insufficiency, or those with very early menopause as a result of total hysterectomy or other causes. There clearly are women who want HRT, even synthetic HRT. Whether for personal quality of life issues or out of therapeutic necessity, we believe women are entitled to make that choice for themselves.
Now let’s turn to the opposite camp’s point of view — those who claim HRT should still be considered safe because the absolute risks are small, a position that’s further justified by the claim that there are no better alternatives. Here are some points to weigh when considering this viewpoint.
- First, there is evidence that synthetic HRT can harm a woman’s health. Alternative practitioners have recognized problems with synthetic HRT for decades, and dozens of studies document its adverse health effects. In fact, it’s disappointing that it took a massive government research program like the Women’s Health Initiative to move the standard of care away from hormones.
- Second, the 2002 WHI data indicated an overall increase in risk for women on Prempro for breast cancer, heart attack, stroke, blood clots, and dementia. Many of the top problems in women’s health are on that list — but again, the participants’ average age was 63, and the risk profile of postmenopausal women in their 60’s and 70’s just isn’t the same as the risk profile of women in their 40’s and 50’s. Each time the data are recrunched or new studies are published, a debate flares up. Most studies have some weaknesses in their design, implementation, and interpretation that skew the findings. All we can say for sure is that the data clearly show that the risk of heart attack or breast cancer is not as great for women who are closer to menopause as it is for women well past menopause — but lower risk doesn’t mean there’s no risk. Even for these younger women, the benefits of synthetic HRT may not outweigh the risks.
- Third, there have always been alternatives to synthetic HRT. Many women don’t even require hormone therapy to soothe perimenopausal symptoms. (As one writer put it, saying hot flashes are the result of an estrogen deficiency is like saying a headache is the result of an aspirin deficiency.) But for those who do, we find most women get better results from bioidentical hormones — meaning forms that are more bioavailable physiologically than the synthetics — for which far more promising safety data are beginning to accumulate. When we started prescribing bioidentical hormones, they were available only from compounding pharmacists. More than 20 years later, there are multiple brand-name bio-HRT products to choose from — in forms that have been well studied and FDA-approved — so conventional health providers now prescribe them.
Why the sense of urgency?
Why learn more about the risks of menopause drugs? For starters, over 13 million women were on some form of HRT in 2002, when the initial WHI hormone data were released. This data revealed a high incidence of adverse events, leading the first arm of the WHI to be discontinued prematurely.
At that time, some eight million American women who had undergone hysterectomy were on synthetic estrogen replacement therapy, mostly Premarin (conjugated equine estrogens, or CEE). Another six million who still had their uteruses were taking a combination of CEE plus a synthetic progesterone, typically Prempro (medroxyprogesterone acetate, or MPA), as prescribed by their healthcare practitioners.
Because Premarin and Prempro were the very drugs used in the WHI hormone trials, and Prempro was the drug used in the arm that researchers had to abruptly discontinue, it’s understandable that many women felt some combination of fear and panic when the headlines broke.
Millions quit “cold turkey” and saw their symptoms rebound. Millions more have remained on HRT, but live in fear of the long-term consequences and short-term side effects of hormone replacement therapy drugs. And millions of other women have been placed on newly designed antidepressants for menopausal symptoms positioned as substitutes for HRT — even though most of these women are not depressed — thereby exposing them to new set of potential side effects.
In the interim, we’ve learned a lot about HRT risks and side effects, but we’ve still a long way to go. When women experiencing symptoms of menopause learn as much as they can about their options, they become their own best advocates, and are better prepared to make informed decisions, gain relief, and enjoy the best of health.
(See our discussion of new findings relative to the Women’s Health Initiative studies — why an individual approach is best).
Potential side effects and risks of HRT
This list of risks observed with HRT use varies by a woman’s age; her environmental, nutritional, and lifestyle factors; and her genetics and medical history. The type, combination, and dosage of hormones used; the route of delivery; and duration of treatment also greatly influence risks.
- Endometrial bleeding
- Breast tenderness
- Increased breast density, higher rates of abnormal mammograms and breast biopsies
- Increased risk of cancers, including breast, ovarian, lung, and malignant melanoma
- Cardiovascular events (e.g., heart attack, stroke, cardiovascular death)
- Gallbladder disease
- Venous thromboembolic events (blood clots)
- Reduced insulin sensitivity
- Brain atrophy, increased risk of dementia, decline in memory and cognition
HRT risk isn’t one-size-fits-all
The bottom line in this debate is that decision-making around menopausal therapies in women is complex. As much as we’d like to say we have all the answers, many aspects of the risks and benefits of menopausal hormone therapy remain unknown. I think we humans are programmed with a healthy respect for the unknown, and continued caution in prescribing hormone therapy to women is prudent.
We’re fortunate to live in times where there is lively debate, and ongoing trials will continue to investigate the timing hypothesis of hormone therapy, as well as effects of various forms of hormones and delivery methods. We will continue to follow these studies, and help women confront their concerns and set their risks in context.
In the meantime, I encourage women, including those on synthetic hormones such as Prempro or Premarin, to consider their options. We always recommend lifestyle and nutritional support, along with targeted endocrine support in the form of phytotherapy to address symptoms of hormonal imbalance.
If severe symptoms continue to disrupt your life, or, if you’re under 40 and have had your uterus and/or ovaries removed or a diagnosis of premature ovarian failure, consider seeing a provider with expertise in compounded bioidentical hormones. At the molecular level, bioidentical hormones are the same as those found naturally in the human female body, and they can be custom-compounded to your specific needs and titrated over time. If you’re unable to find someone knowledgeable about compounded hormones, regular providers can now prescribe one of the many name-brand bio-HRT products available through regular pharmacies.
When switching over from Premarin or Prempro to bioidentical forms of estrogen and progesterone, there is usually a transition period. It is as if the body’s hormone receptors have been blunted by the synthetic molecules and have trouble recognizing other forms, even a woman’s own. When a woman chooses to go off Premarin, I generally recommend that she take two to four months to make the transition and not stop “cold turkey.” If she does stop abruptly, she may experience extreme hot flashes and vaginal dryness, or any of the other symptoms that caused her to turn to HRT in the first place. (Read our article on what to expect when getting off HRT for further guidance).
Women learn to trust their bodies in stages. You begin by reading and increasing awareness. Next comes working with your practitioner to formulate a plan that suits your unique needs, or perhaps finding a more appropriate practitioner. You also move forward in health by improving your nutrition and metabolism, reducing stress, and making time for yourself. These steps unlock your body’s ability to heal itself. It’s never too late to make informed choices, and it’s never too late to begin to heal.