When it comes to medical strategies, one size never fits all. Dosages and directions for use need to be individualized. Genetic factors, current health status, age, diet, exercise and weight play important roles. As do total health outcomes.
Earlier today, I was reading an article* for a project that I am working on and ran across the following sentence:
“Clinicians are interested not only in improving symptoms, but also in total outcomes, i.e. changes in patients’ current and future health due to effects of treatment.” The author, Dr. Michael Blaiss, goes on to explain that not only is the clinical response important, but also, quality of life and cost should be taken into consideration.”
I can think of nowhere where this statement is more important than in the treatment of menopausal symptoms. One size, indeed, does not fit all. Therapeutic strategies should be individualized and address a woman’s specific symptoms, her age, her current menopausal status, smoking history, health history, diet, genetics and preferences. A single tablet is no more the answer than a standardized dose of hormone replacement therapy (or menopausal replacement therapy — MHT — as it is called in other developed nations).
Recently, a group of organizations** devoted to menopause, reproductive medicine and endocrinology convened to issue a new statement about the use of hormonal therapy during menopause. To be entirely honest, this is the first time that I’ve believed such a statement is without bias and was not driven by pharmaceutical interests. It also appears to reflect the total outcomes concept. And so, I wanted to share a summary of a few key recommendations so that you can make an informed decision about addressing your menopausal symptoms.
- Menopausal Hormone Therapy or MHT is [one] of the most effective treatments for vasomotor symptoms but benefits are likely to outweigh risks [only] before age 60 or within 10 years after menopause. It is also effective for prevention of osteoporosis-related fractures in at risk women but again, only before age 60 or within 10 years after menopause.
- While estrogen alone may decrease the risk of heart disease and death from heart disease in women under age 60 (again within 10 years of menopause), similar evidence for combined hormone replacement in terms of heart disease has been found. It neither prevents or increases the risk of heart disease.
- Vaginal dryness? Try local estrogen and not systemic; it is preferred.
- The risk of stroke increases with MHT; patches may offer lower risk.
Contrary to widespread data, the organizations continue to dispute the connection between breast cancer and MHT, however, they do emphasize that current safety data do not support the use of MHT in breast cancer survivors. Finally? the consensus statement emphasizes that the decision to use MHT is complex and must take certain factors into account, factors such as quality of life, health priorities and personal risk factors. Dose and duration must also be individualized, consistent with goals, and in consideration of safety issues.
If you want to learn more about HRT and its risks/alternatives, I’ve been writing about the issue and the data for almost five years now. You can start perusing the archive of information here. Meanwhile, be smart, be vigilant, ask questions. Don’t accept the idea that a pill or a single solution exists; it probably doesn’t. And mostly? Keep the faith. I’ve got your back. Promise.
*Blaiss MS. Cognitive, social and economic costs of allergic rhinitis. Allergy and Asthma Proc. 2000;21:7-13.
** The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, the International Menopause Society, the International Osteoporosis Foundation and the North American Menopause Society.Read More
Back in April, I shared news that researchers would be reporting a strong link between ulcerative colitis and hormone therapy at an upcoming American Gastroenterology Association meeting. That study has now appeared online in Gastroenterology journal so I thought I’d fill in a few blanks.
Ulcerative colitis refers to chronic inflammation of the lining of the colon, leading to crampy abdominal pain, diarrhea and general discomfort. Although it is a form of what doctors refer to as inflammatory bowel disease and is very similar to Crohn’s Disease, it only affects the lining of the colon. I am quite familiar with colitis as a close family member suffers from it and I can assure you that it’s no picnic. In addition to genetics, risk factors include smoking, environment and the use of NSAIDs. And it can be exacerbated by stress, low levels of antioxidants and even milk consumption. It also appears more often in Caucasian whites and slightly more women than men.
Importantly, previous studies have demonstrated an association between oral contraceptive use and risk of ulcerative colitis in premenopausal women, although data are pretty scarse in the older age group who are in menopause. Yet, there appears to be some sort of impact of exogenous estrogen, i.e. not manufactured in the body but taken adjunctively, in that it may modify genes that protect the colon from bacteria and toxins as they pass through the GI tract, thereby exposing women who take them to increased risk.
This has been borne out by data culled from over 108,000 women participating in the Nurses Health Study, one of the largest ongoing research initiatives focusing solely on factors that influence and impact women’s health. After ruling out factors that might influence findings, such as age, smoking and body-mass index, as well as prior oral contraceptive use, the researchers learned that women who had used HRT had a significant risk for developing ulcerative colitis compared to women who had never used HRT. Current users had a greater risk than past users. Moreover, risk increased with longer use of hormones and declined as over time after stopping HRT. It did not appear to matter if hormone therapy was combination estrogen/progestin or estrogen alone.
The researchers write that their findings should be used primarily to provide insight into the possible ways the ulcerative colitis develops. However, even if it is clear that there are many other reasons why women should carefully weigh the risk versus benefit ratio with HRT used, I still maintain that this particular association is as important as others.
In the four and a half years that I have been writing about menopause, HRT has been linked to breast cancer, deaths from lung cancer, ovarian cancer, heart disease, stroke, gallbladder disease and now, ulcerative colitis.
Do the math.
HRT has suffered quite a hit in recent years and as a result, the Menopause Industrial Complex has been scrambling to find a viable replacement. And while I would like to believe in that altruism is driving the train, the cynic in me truly believes that it’s mostly profit motivated. That being said, I do admire the tenacity of industry to attempt to find a reasonable replacement for HRT (and hopefully a safer one) for women who want a fix for troublesome vasomotor symptoms — hot flashes and night sweats — and don’t want to make the effort or don’t understand how to navigate the landscape of alternative strategies.
However, let’s be clear: there is a distinction between nonhormonal treatments and non-pharmaceutical treatments, hence, when you start hearing about ‘nonhormonal’ options, be sure to ask what that means, because it’s likely that it means ‘not HRT,’ such as a new non-hormonal pharmaceutical alternative to HRT: LDMP, better known as low-dose paroxetine. For those of you who are unfamiliar with paroxetine, it is a type of SSRI used in the treatment of depression, panic disorder and social anxiety disorder; the popular antidepressant Paxil is a form of paroxetine.
Paroxetine is not the first antidepressant to be studied in menopausal women and you may recall that I wrote about the use of Lexapro for hot flashes about a year and a half ago. You can find that post here. However, paroxetine is the antidepressant that’s all the buzz right now, since Noven Pharmaceuticals presented two studies last week at the North American Menopause Society annual meeting. Note that it’s been reframed as ‘low-dose non-hormonal therapy for menopausal vasomotor symptoms,’ but ya still gotta call a spade a spade and what it is is an antidepressant.
Here’s what you need to know:
In one of two studies, 568 women (40+ years of age) who experienced 7 to 8 moderate or severe hot flashes on a daily basis of 50 to 60 on a weekly basis took either 7.5 mg of LDMP or placebo daily over six months. By the end of the first month (and in contrast to the study’s start), women who were taking LDMP experienced 28.9 fewer hot flashes per week (compared to 19 fewer per week for women taking placebo pills). By the third month, this increased by roughly 10 fewer per week in both groups. The severity of the hot flashes also significantly decreased. Safety wise, women taking LDMP reported nausea and bronchitis.
In the complementary study, which lasted for three months, 606 women in the same demographic took the same dose of LDMP or placebo. Decreases in mean number of flashes per week were pretty much on par with the first study (33 compared to 23.5 for placebo) and similarly, a trend towards maintaining and growing benefits were observed. Severity of hot flashes also declined but by the study’s end, were not significantly different than placebo. This time, women who took LDMP most frequently reported dizziness and fatigue.
Dr. James Simon, one of the studies’ investigators and a professor of ob/gyn at GWU School of Medicine claims that symptoms of menopause often go untreated when women are unable or unwilling to take hormone therapy, which is not entirely true. Another investigator — Dr. Andrew Kaunitz from the University of Florida College of Medicine in Jacksonville notes that if LDMP is approved by the FDA, “it could be the first nonhormonal option available for women.” Again, this statement is not entirely true. LDMP has the potential to become the first nonhormonal treatment APPROVED by FDA for vasomotor symptoms in menopausal women. There are other options out there but on the most part, they are not embraced by Western practitioners. Take note: while many Western practitioners will argue until they are blue in the face that alternative strategies have no role, are no better than placebo, and do not have evidenced-based trial data to support their use, they are simply incorrect. An unequivocal statement about every alternative strategy available to wo-man is bad medicine at best and at worst? Sheer ignorance.
Back to LDMP…LDMP appears to effectively diminish hot flashes and sweats but it is not without side effects. And while the dosage is considerably lower than full-strength antidepressants, we don’t have enough information to know if it will ultimately mimic its higher dose partner; the most common side effects reported in these trials are the very same that have been reported with Paxil. Another common side effect of Paxil that has not been explored (at least not publicly) in these trials is the effects on libido and it is a well known fact that as many women go through menopause, they experience declines in sex drive, lubrication and the ability to reach orgasm.
I say that the verdict is still out. And that based on the way that communications about this agent are being framed, that it’s about the spin. I guess that time will tell.
Have you heard of personalized medicine? This burgeoning movement in healthcare focuses on the individual and not the masses and relies on our unique biological and genetic profiles to guide therapy choice.
With all the hullabaloo over hormone replacement therapy (HRT), mixed data about risks and benefits and a lack of a clear path for women who choose to go this route, personalized medicine might hold the answer. In fact, in an online review in Metabolism, authors are exploring the very idea that some women may be more ideally suited than others for hormone therapy. Personalized medicine may also make it possible to tailor dosing, formulation and even route of delivery to make the benefit-risk ratio, which we know has been swinging toward the negative, more balanced and favourable.
Although a recent report has come out disputing the role of hormone therapy in increasing risk for heart issues, data from the Women’s Health Study showed that compared to placebo, women who took combination hormones were 24% more likely to develop heart disease (i.e. heart attack or coronary death), up to 40% liklier to have a stroke and twice as likely to develop a blood clot in the lungs. Women who took estrogen only had almost a 40% increased risk for stroke and a trend towards an increased risk for developing a clot in the arteries leading to the lungs. Yet, these results might not be applicable to all as research suggests that factors such as age, time since the onset of menopause, LDL and other cholesterol levels and the presence or absence of metabolic disease may be able to help identify women who are better versus worse candidates for HRT (and likely or less likely to have elevated risk). Moreover, emerging evidence suggests that women who already have an elevated risk for stroke should either avoid systemic hormone therapy or choose a safer delivery method, e.g., a transdermal (through the skin).
A number of experts believe that using lower doses of hormones, bioidentical compounds, and going the transdermal route may very well change the benefit/risk ratio as well, primarily due to reduce blood levels of circulating hormones or as with transdermals, the fact that the drug doesn’t pass through the liver. In some cases, however, the data are scant and randomized clinical trial evidence, also referred to in medical circles as evidenced-based medicine, may be lacking. Still, I do believe that personalized medicine may hold the key for millions of women who can’t find relief through alternative strategies or simply desire more immediate relief. Perhaps some of these very factors that researchers are exploring will remove some of the roadblocks. Meanwhile, pay attention to the variety of factors that may the golden ticket – factors like age, time since menopause, heart health, existing breast cancer risk, biomarkers in the blood and genetic predisposition. Who knows? HRT personalized might be just around the corner.Read More
I ran across a piece in yesterday’s New York Times highlighting that Roche Pharmaceuticals was closing its Nutley, NJ plant where it first developed Valium and its predecessor, Librium. In it, writer Robin Marantz Henig notes that these two agents were actually marketed to physicians as medications that could help individuals feel ‘normal,’ (that is, if normal means walking around in a pleasant fog that masks reality). Henig writes “As Roche closes its New Jersey headquarters, it plans to open a smaller research facility in Manhattan in late 2013, part of a wave that city officials hope will turn New York into a biotech mecca. The company’s transition reminds us of a phenomenon that’s become so common we no longer even think of it as weird: the oxymoronic attainment, through using drugs to make you feel more like yourself, of an artificially induced normal.”
This thought got me wondering if we had actually gone full circle, where the ultimate goal of treatments for menopausal symptoms are to help a woman feel normal again without addressing underlying issues that may be exacerbating how she feels or how her symptoms manifest, things like life stressors, obesity, thyroid imbalances and intimacy problems.
Is HRT (or low dose HRT, which industry has quickly created to replace controversial products like Premarin) soon to be the ‘new normal?’ Granted, the only fog it creates may be the one that removes common sense from the equation in a woman’s quest to replace that which is missing. Ironically, agents like valium and librium similarly took the edge off the very factors likely causing anxiety in the first place.
And so, on a Monday, I pose this question:
What does your new normal look like?
It seems that everything that’s old may very well be new again.