There are few drugs in modern history that have stimulated greater controversy than Premarin. Since its FDA approval in the early 1940s more than 30 billion doses have been dispensed. The estrogens in this hormone replacement therapy (HRT) are made from purified pregnant mare’s urine.
By the 1960s, Premarin was widely prescribed to ease menopausal symptoms. Not only was it used to eliminate hot flashes and night sweats, doctors prescribed it to calm anxiety, slow the aging process and help women stay “Feminine Forever.” That was the name of a popular book written by physician Robert A. Wilson in 1966.
Since then, Premarin has been praised and vilified by doctors, patients and consumer advocates. Even 40 years later the controversy rages on. Epidemiologists continue to argue about the risks and benefits of HRT. On March 7, 2012 an online article in The Lancet Oncology suggested that estrogen by itself (without progestin or medroxyprogesterone) does not increase the risk for breast cancer and might even lower it. The key author (Garnet Anderson) was quoted as saying, “Women who have had a hysterectomy may be reassured that taking estrogen by itself, short term, to relieve menopausal symptoms will not increase their risk of breast cancer.”
Sounds convincing and very reassuring. But 25 days later on April 1, 2012 (not an April Fool’s joke, we assure you), a much larger study was presented at a cancer conference in Chicago with just the opposite results. The research involved roughly 60,000 nurses who participated in The Nurses Health Study. Data was analyzed from 1980 through 2008. Women who took both estrogen and progesterone (Prempro for example) had an 88 percent higher risk of breast cancer after 10 years on the treatment. Those who took estrogen alone for at least a decade had a 22 percent increased risk of developing breast cancer. Those women who were exposed to just estrogen for more than 15 years had a 43 percent greater chance of being diagnosed with breast cancer. The lead author, Dr. Wendy Chen, is quoted as saying, “There’s a continued increase in risk with longer durations of use and there does not appear to be a plateau.”
With such conflicting research and dueling headlines (one month you read that “Estrogen Pills Reduce Breast Cancer Risk” and the next you see that “Long-Term Estrogen Therapy Does Up Breast Cancer Risk”) it is hardly any wonder women are totally confused.
The experiences of individual women often get lost in the clamor.
Some women, like this one, strongly favor the drug: “I had a complete hysterectomy in 1974 due to endometriosis, a very painful disease involving my uterus and ovaries. I took Premarin but did not take progestin since I had no uterus. I have heard that progestin is what may increase the risk of cancer for women taking estrogen.
“Nothing terrible has happened to me all these years on Premarin. At 79, I’m healthy and play tennis and golf regularly.”

Another woman had a serious side effect, but still opts for Premarin: “After I had a hysterectomy, I was put on a high dose of Premarin for menopausal symptoms. I stayed on it for 30 years. Two years ago, I was diagnosed with early breast cancer. I had a lumpectomy and 7 weeks of radiation. The cancer has not returned.
“Would I do it again? You bet! Surgery and radiation are a small price to pay for 30 years of health and happiness.”

Here is a different perspective: “In the mid 1980s, my doctor talked me into taking estrogen for night sweats and lack of sleep. In 1998, after taking estrogen all that time and getting annual mammograms for 12 years, I was diagnosed with early stage breast cancer.
“I needed a lumpectomy and five weeks of radiation. The first thing I was told was to stop taking estrogen. Not long after that, the uproar started over HRT and many women stopped taking it. After 12 years, I was breast cancer waiting to happen. I took it that long because I was told it was good for my bones.
“In 2006 I found out I had uterine cancer. I’d had symptoms for only a few weeks before they performed a hysterectomy. The doctor said the cancer was about to break through the lining of the uterus. I guess I was lucky. Again, I needed five weeks of radiation. This time it was much harder.
“I have to wonder if any of this would have happened had I never agreed to take the estrogen. I guess I’ll never know.”

Proving that HRT was responsible for a particular woman’s cancer is very difficult. The stories of these three women demonstrate why individual preferences must be part of the prescribing decisions. Weighing benefits and risks based on objective information is critical to that process. The latest data from the Nurses Health Study seems to confirm that use of hormones beyond 10 years increases the risk of breast cancer. That includes estrogen by itself or combined with progesterone. Whether so-called bio-identical hormones would be any safer remains to be determined.
For more information about treating menopausal symptoms and hot flashes without estrogen or progesterone, or a combination of the two, we suggest our Guide to Menopause or The People’s Pharmacy Quick & Hand Home Remedies from National Geographic. You can find both in our People’s Pharmacy Store under Guides or Books.

Join Over 52,000 Subscribers at The People's Pharmacy

  1. DG
    Reply

    Hello~ I have posted before about my experience of taking Premarin, then Cenestin, and recently (10 months ago) back on Premarin because the cost of non-horse-urine derived Cenestin is obscene.
    My hysterectomy was 26 years ago at age 33 and I am now 59. I have always had fibrocystic breasts but last week a small nodule was discovered in one breast and micro (the yucky kind) calcifications in the other.
    I am going in for 2 or maybe 3 biopsy/exploratory surgeries in the coming few weeks. I am nervous about what be the findings. So…even though I have lowered my dosage of estrogen over the years am not ready to go cold turkey. I once did for 3 months and I wanted to die..I had depression for the first time ever and noooo energy.
    The only recent difference in my health regimen has been going back to Premarin after using Cenestin for about 12 years with no change in my yearly mammos. I think that subconsciously, I am causing myself stress by taking the Premarin daily KNOWING full well that I oppose animal cruelty to my core and really despise the fact that I am a part of the ill treatment of horses for the selfish purpose of my own wellbeing…I believe in the total mind/body/spirit connection and therefore I have decided no matter what the findings of my biopsies…..I am going to find an alternative to Premarin once again.
    I am on Medicaid now and it doesn’t cover Cenestin…nor does the Canadian Pharmacy carry it….and I cannot rationalize or afford spending over $400 every 3 months for something that ultimately could be part of the cause of my breast situation..though I am not of that thinking at this point. Many of my women friends who have never been on HRT have had similar scares re: lumps and calcifications…..
    SO…I guess my real reason for posting is; Has anyone had to find an alternative brand and type of estrogen??? 2 of my gals are on Estrace (Estradiol) because that is what their Insurance company covers…(are our bodies being controlled by corporate america or WHAT???)…and they seem happy with it. I think I tried it early in my hormone experience and found it didn’t do much for me. I guess I will be discussing it with my Primary Health Provider on Monday when I have my yearly exam with her…maybe she has some suggestions. I would love and appreciate hearing of anyone in my particular circumstances regarding HRT..Any advice is welcome. Thanks all…….

  2. Laurie
    Reply

    Just between you and your doctor, why must you stop taking this now? If it is not a health-related reason, maybe my story will help. I had all the same symptoms you describe, except maybe headaches, before starting HRT. When I reduced my dose during the big HRT scare, only hot flashes (and frequent UTI’s returned). Maybe the bio-identical form would prevent having to wean off? I’ve been on Estradiol gel for 4 months now and feel good. (Sleeping well, good memory, no hot flashes and no more night sweats that I had on 1/4 original Premarin dose.) There were several options for balancing w/ progestins. I picked the one of having a menstrual cycle every 2 months because it feels “safer” to me, so lining of uterus clears itself out. Hope you won’t need to feel sad and have other symptoms much longer.

  3. KKR
    Reply

    I have been taking Premarin 1.25mg since my complete hysterectomy in 2000. At my last physical, in May of this year, my doctor and I decided that I should start to wean myself off of it. She said I could cut the pills in half but since they are so hard, the pharmacist suggested I take one pill every other day. My doctor agreed. Since this time, I have been experiencing hot flashes, memory loss, disrupted sleep pattern, headaches and increased depression. Is this common? Has anyone else experienced the memory loss and depression? I already take an anti-depression medication but, as of late, it just seems to be worse.

  4. GR
    Reply

    I had a complete hysterectomy at 38 years old due to endometriosis and interstitial cystitis in 1998. Even after all these years I still get horrible hot flashes and night sweats. My family has a history of heart problems and arthritis but I have had none of these since being on Premarin. I get regular mammograms and all have been negative. I will continue to take Premarin for as long as I can. Because my prescription ran out and my new gynecologist appointment isn’t until next week, I have been off Premarin for a month and I am MISERABLE with intense hot flashes. I hate it. I constantly feel sweaty and have to dab at my shiny face because of the perspiration. If I couldn’t get my Premarin from my doctor, I would get it illegally some way because there’s no way I would put up with these hot flashes forever.

  5. DG
    Reply

    I totally agree. Same scenario as me.

  6. SC
    Reply

    I have taken Premarin .625mg for over 25 years after a complete hysterectomy. I have had no issues with breast cancer or heart issue. I tried take a lower dose estrogen but I was a wreck mentally and could not sleep. To me it is worth the very small risk to continue my .625mg dose and have a better quality of life.
    I think a study of the effects of radiation from mammograms should be done as far as causing breast cancer.

  7. Franny
    Reply

    Hi,
    Can anyone tell me if I absolutely need to take progesterone (prometrium) as long as I am taking premarin? I am 53 and have been taking both for 4 years to alleviate peri-menopause symptoms. I would like to continue taking premarin for another year or so but don’t see the need to continue taking the progesterone. There is no family history of breast cancer.

  8. Laurie
    Reply

    Hi DG — So far so good on estradiol gel, but will need another six weeks or more to really tell. Because tomorrow I go back to be started on the needed progestrone, to balance the estradiol. (See ref to shell’s note, below — it gives me hope!) :) Fwiw, the new gyn had me go off norethindrone acetate (Aygestin) and Premarin, and switch to just estradiol gel seven weeks ago. The plan is to add in whatever he picks for a progestin and see how that goes.
    Till reading shell’s post, had not realized that some believe it’s the progestins that are ‘feel good’ hormones, rather than the estrogens. (Premarin has many types of estrogens, for example.)
    I did begin to wonder if I felt more “irritable” about a week ago, so reported this to gyn’s office. They immediately put him on the phone (!)and he said to take a couple days off and then start back, using a diff place on body, with thicker skin (lower dose absorbed that way, I imagine.) I felt better right away, so it is also a strong placebo effect and the good feeling of finding a doc who listens and has ideas and is flexible. wow.
    If I forget to post in a month or two, and you’re still wondering about moods, ask again. (I get a feed for this thread of emails.) Oh, yes, did get big improvement in sexual health, more comfy after intercourse, seems better vaginal flora, natural lubrication, feeling well-protected against frequent UTI’s I was getting when I had tried reducing Premarin dose (from 0.325 to half that — admit, I was breaking pills into quarters to get this: 0.160 mg/D… approximately.) :) Will know more about energy issues after progestins are added and adjusted if needed. Good, so far.
    About costs. There are generic estradiol gels on the U.S. market, but the Estrogel does not have a generic. My doc gave a big explanation about how it is not made at a compounding pharmacy. (I suspect he owns stock in Estro-gel. He gave me 2 months’ supply but it will have co-pay on my very good drug insurance of $100 for 3 months’ supply. I know that doesn’t sound like much, considering the benefits of it, but it’s a LOT higher than drugs in the formulary or generics.) The talk he gave me was about the actual dosage that the person receives, per unit or “dose.” Generic concentrations can go up or down, he says, up to 10% per year, and still receive FDA approval. Because his Estro-gel has a more steady dosage, year to year, he feels it’s a better drug. Frankly, I do not agree.
    A gel, even w perfect “pump” dosing, can vary in absorption and even dosing, depending how much stays on your hand instead of on skin where applied. And we’re supposed to wash our hands well after application (thus lose a little gel) so as not to expose other people to estradiol. (Esp. males and children.)
    Sorry to ramble, but I believe a less expensive generic estradiol could be very effective for all the good reasons: bone mass, vaginal and urinary tract, oxygen to the brain (I believe estrogen may facilitate neuron cell oxygen uptake, read about it some place.)
    Can’t wait to see if the progestin makes me even happier than now! And hope to hear from more people, since I’m just one out of many on HRT. Gotta add that I was afraid of gaining wt. from stoping Premarin and Aygestin, but so far, not happening. I walk almost every day on a treadmill and the very very slow wt. loss I was hoping for has gone very well. I put on about 20# during menopause and managed to loose more than half of it, over past 8 years. This works for me. : ) p.s. I’ll be 66 this month, on HRT since age 43. They talked me into it because of osteopenia, but still have that, even after 12 years on Fosamax. (Off it for 2 years now.)
    Let me again highly recommend reading shell’s entire post of April 5, 2012 (found it when skimming down posts today) which in part reads,
    “Progesterone is the “feel good” hormone, as it acts as a “natural anti-depressant,” boosting moods and well being as well as stimulating bone growth, healthy heart function and offering protection against breast and uterine cancer. ”

  9. shell
    Reply

    Not sure whom you are asking but as for me – yes I like the Estradiol Gel. And yes I am getting the same benefits and yes it helps vaginal health and mood, energy issues, etc. as well as the Premarin did.

  10. DG
    Reply

    Hi there~ I have been on HRT (estrogen mainly with a tiny bit of progesterone compounded cream at bedtime…) since I was 33 when I had a complete hysterectomy… I am 59 so that makes 26 years?? I have, over time, gone from 1.25/day to 0.62 mg/day… and was using Cenestin for the past several years but had to switch back to Premarin because of cost and no insurance… buying the Premarin now from a Canadian Pharmacy online which really saves me a lot of $.
    When I tried going off HRT for 3 months many years ago… I got very depressed for the only time in my life and had vaginal dryness (yeast infections), lethargy, flattened breasts… you name it. I went back on and have been ever since. I tried all the other forms of estrogen… ogen, estrace, etc etc… even the patch, available at the time 2 decades ago. Premarin was the only one I liked.
    I am interested in hearing more about this Estradiol Gel?? Are you getting the same benefits that you got from the Premarin?? Does it help with your vaginal health and mood, energy issues, etc. as well as the Premarin did? Thank you for any info you can share. I know a woman who is 88 and still on HRT since her menopause… Premarin and Progesterone tabs… and the only real issue she has is macular degeneration… and a bit of foggy mind… which I attribute more to not being able to see properly and navigate in our world… I mean 88!?! No cancer… no heart attack… no stroke… The only thing that worries me about me is these yearly mammograms… Have had them since the hysterectomy!! But Doc may cut them down to every 2 years at my request. I have cystic breasts but never have had to have a biopsy. I probably glow in the dark from radiation!! ;)

  11. Laurie
    Reply

    Hi — why does your doc want you to quit? Maybe they’d feel better about so-call “bio-identical” estradiol, even comes in gel form. I was on Premarin and Aygestin for over 20 years and read the women’s health initiative study in detail.
    For me, the risks did not outweigh benefits.(I’m not hi risk in any category except osteoporosis, so docs are more easily swayed to let me stay on the drugs.) A new gyn recently switched me to estradiol gel and I am getting more benefits and no apparent side effects, btw.
    He says research shows this formula is better to prevent bone fractures than Premarin. The actual studies of HRT show a very small number of cases leading to impairments or death, however researchers and drug companies do not want any of us to be the one who might be harmed by their products. Hope to hear more from others. And how Gillie is doing. : )

What Do You Think?

Share your thoughts with others, but be mindful of protecting your own and others' privacy. Not all comments will be posted. Advice from web visitors is not a substitute for medical attention. Do not stop any medicine without checking with the prescriber. In posting a comment, you agree to our commenting policy and website terms and conditions.