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Getting off Prempro–Updated

August 28, 2007

“Can we twalk?” –Joan Rivers

If you have read this before and found it at all helpful, please read the updated Addendum at the end.  

Note: I’m posting this not because it’s interesting, or because I’m flamboyantly concerned with sharing this information with every male peer I have in the world, but primarily for the sake of my female friends and those who don’t know me at all whom search engines might direct here. This is not about the epidemiology of HRT; it’s not a parametric study at all. I am simply recording an outline of my personal experience. I know a lot of searches are conducted for this sort of thing, so if that’s why you’re here, I hope you find it in some way helpful.

Life is a calculated risk, and ultimately we have no control over the algorithm.

“…without the will of my heavenly Father, not a hair can fall from my head…” (Heidelberg Catechism, Ans. 1)

We are provided with means of mitigating disease and unpleasantness, and it is reasonable to avail ourselves of these. When I began taking Prempro in 1997, I considered four factors that were then state-of-the-art empirical pooh-bah. At the time, the drug was believed to lower cholesterol, end hot flashes, retard bone loss, and preserve memory and intelligence. Other concerns were a minimal risk of stroke and a fairly elevated risk of breast cancer, but I had no other risk factors for either of these. In any case, I figured cancer was curable; I was concerned with present symptoms, not future hypotheticals. As for strokes, the risk was believed to diminish after two years of stroke-free living.

My cholesterol level is considered high-risk; I was having hot flashes every few minutes around the clock, diminishing my quality of life considerably, and my mother had osteoporosis and Alzheimer’s. My image was clearly the stuff of HRT posters.

It took a few formulary tries before my then-doctor–blessedly, the most intelligent and diligent doctor I’ve ever had in my life, but no longer practicing where I live–arrived at Prempro. He had hoped for something “lighter,” but nothing else ended the heat episodes. By “lighter,” I mean lower steroid content. Progesterone can be heady stuff for the uninitiated.

I was totally uninitiated and have always been very sensitive to medications. The four-hour-long mental crash that hit within an hour or two of my first Prempro pill was a trial my husband and I will never forget. My friend Deb and I would later laugh when I recapped my obsession with trying to call her to send a helicopter to get me to help. Fortunately, I was too debilitated to dial the phone. My husband just held on to me and kept saying, “We’ll get through this” for four hours.

We did, and the hot flashes ended and I had no more side effects, at least none that I attributed to Prempro. My cholesterol continued to rise every year, especially my evil LDL. Genetics and my light frame won the battle of the bones: I developed osteoporosis in my 40s.

Cancer and stroke risk diminished even in theory, but a new doctor demanded that I sign waivers to stay on Prempro longer than two years. I signed them. It isn’t easy finding what they used to call a doctor.

I fought cholesterol with disbelief in its perils, and took Actonel for bone replacement. I can’t really know whether my intelligence and memory are intact, but I’m well below the age of worry on that score, at least given my mother’s experience. In any case, faithful science is working on a pill for Alzheimer’s. We Boomers will demand mental immortality, and the pharmaceutical industry will want to sell it to us.

Later studies became the stuff of headlines, and researchers reversed themselves continually. They decided that cancer and stroke risk were always elevated with Prempro. I was glad I’d already dumped my Wyeth stock, but I wouldn’t dump my Prempro.

I tried once, after taking the drug for six years. The depression and confusion were immediate. I didn’t skip a day again for almost four years.

Dovetailing into the Prempro era was the migraine phase. It isn’t possible to know whether the Prempro was in any way causal. Some people do develop migraines while on HRT, and the migraines cease when HRT is ended. My migraines began three years ago, but no one recommended going off Prempro to curtail them. Depakote finally brought the daily migraines under control. Then, after a year of fewer migraines they again began occurring daily. I went off Depakote and the migraines stopped, or at least backed off to being occasional. It seemed that at some point, a switch occurred in my system so that Depakote began to cause the symptoms it had formerly repressed. My system cued me in the same way when it was time to go off Prempro.

It wasn’t something I noticed immediately, because I have always been sensitive to heat and sun, but about a year ago, I realized I didn’t sweat, not ever, not at all. I live in a fairly humid climate, so it isn’t merely a case of instant evaporation. Since my cardiovascular condition is stronger than my orthopedic capability, I thought it was due to the fact that I simply couldn’t exercise hard enough, because of back and knee pain, to sweat. Even walking on my treadmill at 3 mph in a 76-degree room brought on only a slight clamminess. The trouble is that I become very hot, but can’t perspire. And I was becoming very hot a lot of the time, even sitting down in our air-conditioned home.

A little research revealed that I had symptoms of heat exhaustion much of the time, even without exertion. I also learned that some medications will cause anhidrosis (inability to sweat), but no HRT medications were listed among the suspects. Still, the list is not likely exhaustive, and I suspected that Prempro, once a wonder-drug that kept hot flashes at bay, was possibly behind the heat episodes and the anhidrosis. As was apparently the case with Depakote, Prempro had possibly begun to induce symptoms it had once controlled. But  without the ability to sweat, I faced the new danger of heat stroke.

I didn’t de-titrate. I forgot to take my tablet once and felt better. I skipped it another day. Nothing changed, so I stopped taking it. This time there was no depression and confusion. The hot episodes still occur, but they did before. Maybe normal sweating will return. It seems that after ten years, my system became, in a sense, HRT-indifferent.

HRT is marketed primarily for symptom relief. The other benefits touted at the time I began the regimen were billed as supererogatory. As for risks, I don’t give much credence to the HRT studies I see, because one study inevitably gainsays another. In any case, extrapolation from small cohort studies is dubious.

That notwithstanding, some recent studies suggest that HRT actually elevates triglyceride levels. Others suggest that there is a positive correlation between HRT and dementia, rather than the reverse. And it seems that HRT may have nothing to do with bone loss one way or the other. It works to quell hot flashes in most people, and many, myself included, swear by it as a mood stabilizer. But the mood swings might have gone away in a week or a month or a year; all I’m saying is that in my case, the fear of the moods and hot flashes outweighed the fear of future disease.

Women in their 40s are more likely than anyone else to develop chronic fatigue and sicca syndrome (extremely dry eyes and mouth, without antibodies dispositively indicating Sjogren’s Syndrome). Whether HRT promotes this is unknown. I developed both conditions after commencing HRT, but I was also at the typical age of onset for these syndromes, and had a medical history consistent with their development.

Spurious correlations abound in medical studies and in anecdotal lore; they become the stuff of urban legends. “Studies” are an imperfect source of information. After all, the trend in refrigerator prices correlates positively with the proliferation of feral cats in suburban parks, too.

I have no regrets about staying on Prempro for ten years. I’m relieved I had no trouble finally going off it. I’m grateful I don’t have to make the HRT decision now, and especially grateful I never had to make it for anyone else. Hype and paranoia surround a lot of good things, and a lot of bad things are used recklessly. I think the most important thing to keep in mind is that probabilities, while potentially useful, don’t predict individual outcomes.


September 15.  I have been back on Prempro for a week.  After being off it a month, I began experiencing disturbing lapses in judgment and concentration and decided to resume HRT.  The hot flashes began while I was on Prempro, and continued unabated while I was off it.  They continue still, along with other symptoms.  It appears that I actually have adrenal exhaustion, and that my cortisol level may have suppressed the estrogen, causing the breakthrough hot flashes.  This is educated conjecture; I have not had my cortisol level measured. 


In October 2007 I was diagnosed with Addison’s disease (chronic adrenal failure), following an ACTH-stimulated cortisol test by an endocrinologist.  In the course of the blood work-up, I was also found estrogen-depleted, even though I had been on Prempro for 10 years.  The doctor prescribed Premarin in addition to Prempro, and within three weeks, the hot flashes subsided completely, and I’ve had no further symptoms.  The anhidrosis may have been due to cortisol insufficiency; that, too, is history. 

For years, I had asked doctors whether I was getting the proper amount of estrogen.  “Oh yes.  Prempro is the perfect amount for you.”  Don’t settle for that!  No one has any idea what is enough without testing your FSH level.  But I have to be grateful for the hot flashes for signaling that something was wrong, getting to an endocrinologist, and learning I had Addison’s, which, untreated, is fatal. 

  1. Mindy Boudreau permalink
    September 15, 2010 8:41 am

    Could you tell me if you are currently taking Prempro? If so, what strength are you on?

    Thank you.

  2. September 15, 2010 8:46 am

    Please use the Contact Form on my Authoress page, and explain the reason for your question.

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