NAMS: 'Take the Fear Out' of Hormone Therapy JoAnn Pinkerton, MD, breaks down the highlights of NAMS updated position statement

PHILADELPHIA --  This June, The North American Menopause Society released an update to its 2012 position statement on hormone therapy (HT), published in its journal Menopause and endorsed by dozens of national and international medical societies, including the American Association of Clinical Endocrinologists, Academy of Women's Health, and more.

I caught up with NAMS Executive Director JoAnn Pinkerton, MD, at the group's annual meeting to discuss what she wants all providers to know about HT.

 

MPT: Who is an ideal candidate for HT? Who is not an good candidate?

Pinkerton: Women who are having bothersome menopausal symptoms -- hot flushes, night sweats, sleep disturbances, mood disturbances -- who are close to menopause, ideally under the age of 60 and within 10 years of menopause. That's the woman who's going to get the best benefits and have the fewest risks. An "un-ideal" candidate would be someone who is 75, has not been on HT, and all of a sudden has sweats and is in your office, and you need to figure out why they're having sweats -- number 1 -- which may not be related to menopause at all. And number 2, is if you were to initiate therapy at age 75 in someone who likely already has plaque in their vessels, or changes in their brain, you would be potentially accelerating cardiovascular disease or the risk of dementia.

MPT: Should patients or providers initiate the conversation?

Pinkerton: I would ideally like both to initiate the conversation. I think that many providers are busy, and if women don't complain and say "my symptoms are bothersome," then the provider may not think about using this medication. The truth is that women going through menopause need to have somebody ask about their symptoms and suggest therapy, if it's indicated, and go through risk and benefits. And at the end of the day, it's an individual decision, it's shared decision-making, so I would like the conversation to come on both sides.

MPT: What are the top treatment benefits?

Pinkerton: It relieves hot flushes -- it's the gold standard, as well as sleep disturbances. And then, it also improves sleep duration, it shortens sleep latency, and fewer sleep disruptions and more REM sleep, so that helps the symptom of fatigue and irritability the next day. It also prevents bone loss and prevents fractures. The WHI [Women's Health Initiative] showed a 33% decrease in hip fractures. It can also treat vaginal symptoms, although we can also use vaginal therapy just for vaginal symptoms.

MPT: What are some of the biggest misperceptions surrounding HT?

Pinkerton: Women believe the boxed warning. If I take this, it's going to give me heart disease, breast cancer, stroke, and probable dementia. And we need to say that those risks were found in an older population taking the combination of estrogen and a progestin. But that we have newer doses, lower doses, newer formulations, and we didn't see those risks in the women under 60 and within 10 years of menopause.

MPT: What exactly is the "timing hypothesis"?

Pinkerton: The timing hypothesis is that women who are just becoming menopausal are less likely to have plaque in their vessels, or these white matter changes in the brain, and therefore if you give hormones, it may actually help prevent atherosclerosis or help slow some of the brain changes. Once women have atherosclerosis in their vessels or these white matter changes in their brain, if you give them the estrogen, it may accelerate that. So it's very difficult to prove the timing hypothesis because if you prevent something that now doesn't happen 10 years later, it's hard to actually show what's going on. So the timing hypothesis is that -- it's an unproven, but believed theory.

 

MPT: When is transdermal HT recommended?

Pinkerton: Transdermal therapy is exciting because we have so many different forms. We have patches, gels, sprays, and vaginal rings -- and so number 1 is patient choice, so if patients want to have transdermal estradiol. Number 2, it bypasses the first pass hepatic effect, so that it is less likely to cause risk of blood clots or stroke. So women who have liver disease, if they're still candidates for hormones, women who have fatty livers, metabolic syndrome, anybody where you would want to avoid that first pass would be a great combination. Women who are a little bit higher risk for blood clots, but not so high you don't think they should take it, then that might be another group to think about it. Also women as they age, because our risk of blood clots and stroke goes up as we age, so taking a transdermal, lower dose might be safer.

MPT: How common, or uncommon, is the associated risk for breast cancer, and should this factor into prescribing?

Pinkerton: We think that it's very important that clinicians ask about breast cancer risk, about breast density, about family history, because breast cancer is 1 out of 9. It turns out that in the WHI, when you took the oral conjugated estrogens at .625 and added a synthetic progestin MPA 2.5 daily, that after 3-5 years, we started to see this increase in breast cancer -- it was a very small increase in breast cancer, even though it was quoted statistically, the actual amount is .08 out of 100, so very small risk. That risk might increase over time, and we think that it is real. It was not found in the women who had not used estrogen before they started on the trial, so it's very confusing. It's a risk, it's a small risk, and there's ways to minimize that risk.

MPT: What are some concerns regarding compounded bioidentical hormones?

 

Pinkerton: In 2002, after the release of the WHI, everyone became very fearful about hormones. There was a lot of media hype and celebrity hype that you could take a compounded product and it would have no risk, or if it had estriol, it might prevent breast cancer. And so many women went to something that they thought was safer based on the hype. In reality, we now know there are unique risks of compounding -- overdosing, underdosing, contaminants, sterility, lack of a label, and lack of scientific studies. They're not tested, they're not proven, and they don't go through the FDA approval process or the monitoring process. And so we had the 64 deaths from contaminated intrathecal steroids, and as they looked at other compounding pharmacies, they found that sterility was an issue. And then MORE magazine took 12 compounded Tri-Est prescriptions, blinded them, sent them to a lab, and found that the range of estrogen was anywhere from 69% to 269%, and the progesterone, which was transdermal, not well absorbed, was never more than 60%, putting you at risk for endometrial cancer. We worry about risk to woman taking these products, and we have so many FDA-approved therapies.

MPT: How should we look at women with early menopause differently?

Pinkerton: In the past few years, observational data has found that women with early menopause, particularly surgical menopause but also natural menopause, have health risks associated with the loss of estrogen, and those include cardiovascular, osteoporosis, mood, sexual, Parkinson's, cognition, even some eye changes, that if women are given estrogen at least until the average age of menopause, that puts them back into the general risk population. The WHI does not apply to early menopause, and women with early menopause have an increased health risk due to loss of estrogen, and we recommend, unless there's a contraindication, that they be given hormones at least until the average age of menopause, and then reevaluate what you decide to do.

MPT: At what age should HT be stopped?

Pinkerton: There is no longer a hard stop date. After the initial study from WHI, it was like you could only take it from 3-5 years because of the risk for breast cancer -- now we know that's a small risk and there are ways to minimize that risk. In general, many women will take it for 3-5 years, they transition through, they go off, and they're fine. But other women have persistent symptoms. Up to 15% of women can have persistent symptoms, or they want to use the hormones to prevent bone loss, or quality of life. There's nothing that says you have to stop at 60, or 65 -- that's a fallacy, there's no science to support that. What we have is very limited data about long-term risks, and again, we think about minimizing the risk, and we ask clinicians to individualize it. And each year, assess where's the women, what new risks does she have, what risk does she have from taking it and not taking it, to sort in making a judgment call.

MPT: What's the main message you want providers to walk away with?

Pinkerton: Hormone therapy at menopause for women who are having symptoms is safe and effective for the majority of women, and we have new ways of giving it, new options. Please have the conservation, take the fear out of the room and use the science and evidence we presented in our position statement to help you have a conversation about whether or not a women needs it and what's the best choice for her. And then individualize what you give her, how you give it, and how long you give it to them.

FDA Approves Secnidazole (Solosec) for Bacterial Vaginosis

The US Food and Drug Administration (FDA) last week approved an antibiotic called secnidazole (Solosec, Symbiomix Therapeutics) for women with bacterial vaginosis.

Secnidazole is the first single-dose oral treatment for bacterial vaginosis, the most common vaginal infection in women aged 15 to 44 years, according to the Centers for Disease Control and Prevention.

A dose of secnidazole comes in the form of a 2-g packet of granules. Patients sprinkle the granules on applesauce, yogurt, or pudding and eat the mixture within 30 minutes without chewing or crunching the granules.

Most current antibiotics for bacterial vaginosis must be taken for 5 to 7 days, and often more than once a day. As a single-dose treatment, secnidazole promises to improve adherence and the likelihood of a cure, Symbiomix Therapeutics stated in a news release.

The FDA determined that secnidazole was safe and effective on the basis of two randomized, placebo-controlled clinical trials involving 333 nonpregnant women up to age 54 years. Both trials had three endpoints:

  • A combination of a normal vaginal discharge, a negative test result for amine odor after adding a 10% potassium hydroxide solution to a vaginal-discharge sample, and less than 20% of epithelial cells of the vagina being covered with bacteria (so-called Clue cells).  Someone with all three outcomes was defined as a clinical responder.

  • A "Nugent" score of 3 or lower for the presence of various bacterial cell morphotypes — specifically, large gram-positive rods, small gram-variable or gram-negative rods, and curved gram-variable rods. Such a score indicates a cure.

  • A clinical responder who had a Nugent score of 3 or lower. This score qualified the patient as a therapeutic responder.

One trial assessed these endpoints 21 to 30 days after treatment. The other trial assessed them 7 to 10 days afterward. In both trials, a far higher percentage of patients who took the single dose of secnidazole qualified as both clinical and therapeutic responders and experienced a Nugent-score cure compared with patients who received the placebo.

Vulvovaginal candidiasis, headache, nausea, dysgeusia, vomiting, and diarrhea were among the most common adverse events observed in the two studies. The drug's label warns that vulvovaginal candidiasis associated with the use of secnidazole may require treatment with an antifungal drug.

The agency also warns about the potential risk for carcinogenicity because mice and rats treated chronically with drugs structurally related to secnidazole have developed tumors. "It is unclear if the positive tumor findings in lifetime rodent studies indicate a risk to patients taking a single dose of Solosec to treat bacterial vaginosis," the label states. "Avoid chronic use."

The drug is not recommended for women who are breast-feeding. If they take it, however, they should discontinue breast-feeding for 96 hours afterward.

The label for secnidazole is available on the FDA website.