Hormone Replacement Therapy adverse effects, HRT - Alternatives, natural herbs and Chinese herbal remedy
January 3 2019

Guidelines
Women who have gone through menopause are recommended to avoid using female hormones to protect against osteoporosis or diabetes. The overall benefits from taking hormones to prevent chronic conditions are outweighed by the harms and side effects. This is for all types of hormone replacement therapy, including pills or patches containing either estrogen or an estrogen/progesterone mix. However, those going through menopause can take short-term advantage of hormone replacement therapy to reduces symptoms such as hot flashes and vaginal dryness.

The estrogen most commonly prescribed for women as hormone replacement therapy HRT after menopause is Premarin derived from the urine of pregnant mares (horses). The progesterone prescribed to most women is synthetic progestin. A recent big drop in breast cancer cases might be due to millions of women going off hormone replacement therapy. Hormone use plummeted after a 2002 study found that it raised the risk of breast cancer, heart disease and other problems. Using HRT for several years increases the risk of heart and vascular events and blood clots. It not only increases the risk of first-time breast cancer, it also makes recurrence of the malignancy more likely.
   Hormone therapy helps with menopause-related symptoms such as sleep and memory problems only if a woman also has hot flashes, according to North American Menopause Society, news release, Nov., 2013.

Adverse effects of HRT, potential problems and concerns
Blood clot
J Thromb Haemost. 2014. The risk of recurrence in women with venous thromboembolism while using estrogens: a prospective cohort study. Women who had their first venous thromboembolism while using estrogens have a low risk of recurrent VTE. These women might not benefit from extended anticoagulant therapy.

Breast cancer
Women who take hormone replacement pills are more likely to die from breast cancer. Journal of the American Medical Association, 2010.

Women who develop breast tenderness for the first time while on hormone replacement therapy may be at increased risk of invasive breast cancer. Arch Intern Med 2009.

Hair loss, thinning
Email - I am a 43 year old female. I started HRT (testosterone and progesterone) the summer of 2014 for mild pre menopause systems. When I went for my follow up my doctor increased my testosterone and gave me 5mg of DHEA supplement. 2 weeks after starting the higher does of testosterone and the DHEA my hair started falling out in clumps. I didn't make the association and took the DHEA for 36 days. It has been 5 weeks since I stopped everything and my hair is still falling out at a crazy rate. Can you please let me know if my body is ruined forever? I am so scared, I cry everyday. This has ruined my life!! I feel so stupid and can't believe I did this myself.
   A. In many cases after stopping the hormone treatment hair begins to return, however each person is different and it is not easy to predict.

Heart attack risk
Dr. Kanaka Shetty from the RAND Corporation in Santa Monica, California has found that as the use of HRT has fallen in recent years, so too has the incidence of heart attacks in older women. In 2002, the Women's Health Initiative found that HRT use increased the risk of heart attacks among healthy postmenopausal women, leading to a sharp decline in its use. HRT usage rates among women aged 50 to 69 years remained fairly steady in the mid-1990s and then declined sharply in the 2000s, following the pivotal report on HRT, from over 30 percent of the population in 2001 to less than 15 percent in 2005. Rates of heart attack declined steadily over this period with a sharper decline in the post 2001 period, especially among women aged 50 to 59 years. Medical Care 2009.

Hormone replacement therapy (HRT) does not protect most postmenopausal women against heart disease and may even increase their risk of stroke.

Lung cancer
Women who have used hormone replacement therapy combining estrogen and progestin have a higher risk of lung cancer than non-users. Journal of Clinical Oncology, 2010.

Meningioma associated with hormone replacement therapy
Multiple lines of evidence link meningioma with female hormones, including expression of estrogen and progesterone receptors and higher incidence in women and in patients with breast cancer.

Ovarian cancer
Women who use HRT for only a few years are more likely to develop the two most common types of ovarian cancer, compared to women who had never taken HRT. Those types are serous epithelial and endometrioid ovarian cancer. Short term HRT use, thus far, is not linked to an increased risk of the other two main types of ovarian cancer: mucinous and clear cell ovarian cancers.

HRT effect on physical decline with age
Older women on hormone replacement therapy do not seem to gain any protection from disability as they age. There has been speculation that waning estrogen levels may contribute to muscle loss and other declines in physical function as women age. Muscle cells have receptors for estrogen, and some research has linked higher blood levels of the hormone to greater muscle strength in elderly women. However, a study did not find HRT to be helpful in preventing physical decline in older women. Menopause, February 2010.

Natural hormone replacement therapy and treatment
This is achieved by using natural bioidentical hormones. Another option is to use over the counter hormones such as pregnenolone and DHEA. Still, some people may consider the use of phytoestrogens in herbs or extracts such as isoflavones as natural hormone replacement therapy.

Q. There is considerable information coming my way about Natural Hormone Replacement Therapy, including Testosterone for women. Do you recommend this? Is there over the counter supplements that would be worth trying instead of compounding formulas from physicians and pharmacies?
   A. The whole issue of hormone replacement therapy is very complicated and there are no clear answers of which hormones and in what dosages are helpful or harmful. Each woman is different. Some may benefit from traditional estrogen / progesterone hormone replacement therapy, others may benefit from natural hormone replacement therapy with bioidentical hormones, still others may benefit from the use of natural herbs. It is also quite possible that health is harmed by taking hormones, particularly for prolonged periods.

In vitro estrogenic activities of Chinese medicinal plants traditionally used for the management of menopausal symptoms.
J Ethnopharmacology. 2005.
The estrogenic activity of 32 traditional Chinese medicinal plants, selected according to their reported efficacy for the treatment of menopausal symptoms, was assessed. Polygonum cuspidatum had the highest estrogenic relative potency followed by Rheumpalmatum, Cassia obtusifolia, Polygonum multiflorum, Epimedium brevicornum, Psoralea corylifolia, Cynomorium songaricum, Belamcanda chinensis, Scutellaria baicalensis, Astragalus membranaceus and Pueraria lobata - kudzu. This study gave support to the reported efficacy of Chinese medicines used for hormone replacement therapy.

When to appropriately use HRT
Systemic HT is an most effective treatment for most menopausal symptoms, including vasomotor symptoms and vaginal atrophy; however, individualization is key. Progesterone therapy may be necessary to prevent endometrial cancer when estrogen is used systemically in women with a uterus. Local estrogen therapy is effective and preferred for women whose symptoms are limited to vaginal dryness or discomfort with intercourse; low-dose vaginal estrogen therapy is recommended in this setting.

Controversies - response to the January 2009 newsletter
We had an unprecedented number of email responses to the newsletter. Here is one example: "The January 2009 newsletter discusses the disastrous effects of conjugated equine estrogens and synthetic progestins uncovered by the Women’s Health Initiative study in terms of increasing breast cancer risk, but you seem not to make a major distinction with natural bio-identical hormones. My understanding is that the WHI did not study the use of bio-identical human estrogens and progesterone at all. Everything I’ve read indicates that they have a completely different effect on women’s bodies, and in fact progesterone (the real thing, not synthetic progestins) may be protective against breast cancer. I think you should distinguish between the two."
   Over the past few decades doctors have prescribed horse-derived estrogens and synthetic progestins to women in order to relieve menopausal symptoms and as a way to potentially reduce the risk for osteoporosis or heart disease. A few years ago doctors began suspecting that, in many or most women, the harm from this treatment in terms of increased breast cancer risk and heart disease outweighs the benefits. Many women stopped taking these medications, others turned to herbs and supplements, and still others turned to natural hormones such as bioidentical hormones. Many of you may not be familiar with this term. Bioidentical hormones differ from traditional hormone replacement therapy since they are chemically identical to hormones found within the body -- such as estradiol, estriol, and progesterone -- rather than molecules that are similar, but not identical to human hormones (such as Premarin, derived from the urine of pregnant horses) or synthetic progestins (such as medroxyprogesterone). Many women believe that these bioidentical natural hormones are safe, or safer. These bioidentical hormones are promoted by compounding pharmacists, some alternative medicine practitioners and even one celebrity, Suzanne Somers. Estradiol is also available in many FDA-approved pills, patches, creams and gels from traditional pharmaceutical companies. Is there evidence to support the safety or superiority of bioidentical hormones over standard hormone replacement approaches? I will focus most of this newsletter on this issue.
   Here are some of the emails we received and my responses.

Q. I think your information is great, but I strongly disagree regarding estrogen / progestin. First of all, both Premarin and progestins should be against the law, as we women are not horses and synthetic progestins are carcinogenic. However, bioidentical hormones are a different breed and I have been on them (low dose) for the last 5 years. I don't even think about cancer. I eat a very strict, clean, mostly organic diet and go to an MD who knows what he's doing. Yes, Western medicine is the problem---still giving women Premarin and progestins---it's a disgrace how mishandled most women are today at the hands of misinformed and arrogant doctors who don't want to learn what's new and better.
   A. All doctors, including me, are fallible and have the potential to make mistakes or give wrong advice. In the past few decades many doctors were just as assured and complacent of the safety of hormone replacement therapy with PremPro as many bioidentical hormone promoters are today. There are currently no long term studies with bioidentical hormones to prove their safety.

Q. Dear Dr. S, the horse urine estrogen and synthetic progestin that have been fed to women world wide has been the problem, not bioidentical estrogen and progesterone. The scientific analysis of these products is very clear. Additionally, the very large studies that recalculated their data did point out that the addition of the synthetic progestin seemed to be a large factor in the negative effects. I am 63, was never able to take the horse urine product without feeling ill, so I didn't, even after my hysterectomy at 33 with the inevitable negative results for my bones. Five years ago, my doctor started me on a bio-identical estrogen patch, along with additional magnesium and bio-identical topical progesterone cream. My annual DEXA scans have shown an amazing gain in bone strength, this includes both hip and spine. I no longer expect to end up with dissolving bones which is what other doctors have stated is the fate of most people who live to be very old. Since people in my family lines normally die between 85 and 95, I have been concerned about osteoporosis because the folks who did die earlier usually died from the results of a broken hip. It wasn't fast, usually a year, and it wasn't pleasant and isn't solved by hip replacement. The fact is, bio-identical estrogen and progesterone protect your bones from osteoporosis. The incidence of some form of osteoporosis in the aged is very high. Which means MOST people will get osteoporosis. MOST WOMEN DON'T GET CANCER.... MOST WOMEN DO GET OSTEOPOROSIS. A relatively low percentage of women get cancer and die from it.
   A. This email summarizes one of the basic dilemmas regarding the benefits versus the risks of hormone replacement therapy. Does the benefit of decreased bone fractures outweigh potential harm from an increased cancer rate, heart attack, stroke, or other problems that are related to hormone replacement therapy? Science does not have the full answers at this time.

Q. In your Jan. 2009 newsletter, you site an MSNBC news article that reports taking menopause hormones for five years doubles one's risk of breast cancer. The article clearly stated that the hormones studied were horse estrogen and synthetic progestin ingested by mouth. This is quite different than applying a cream of bio-identical hormones. It may be that these creams increase the risk, as well, but that is not part of the referenced study, and many contemporary studies indicate otherwise.
   A. Until long term studies are done testing bio-identical hormones in terms of their effect on breast cancer and how they compare to synthetic progestins and conjugated equine estrogens, it is premature to claim that one form has less risk than the other. What if bioidentical hormones end up being even more potent in stimulating certain cancers than synthetic progestins or equine estrogens? It took decades for the medical community to find out the full risks of hormone replacement and it may take a long time for women who are currently taking bioidentical hormones, under premature safety assurances by many natural hormone marketers and promoters, to find out that these medications have risks that we are currently not aware of. I did mention in the newsletter that if you were to use hormones as symptomatic relief for menopausal symptoms, my impression is that it would be preferable to use natural hormones. If you are aware of long term studies regarding the safety of natural hormone use, please let us know.

Q. I received Dr. Sahelian’s January 2009 newsletter article with his comments on using estrogens and progestins to help with menopause symptoms. I feel it is very important to point out that the HRT used in the WHI study contained horse estrogen which is not the same as human estradiol now available in products such as Estrace and the Vivelle patch. While the horse estrogen does bind to human estrogen receptors, it does not have the same action as the human estradiol, ie. It fits in the lock but you can’t turn the key. Also, since the human body doesn’t have the enzymes necessary to break down the horse estrogen, it can stay in the body attached to the receptors for several months. Human estradiol is essentially out of the body in 2 days after you stop treatment. I have read several books and studies indicating that replacing a women’s estradiol with the so called bioidentical estradiol is very beneficial. I personally have found this to be the case.
   A. Scientists do get important clues by studying the effect of these hormones on receptors in a laboratory, but until actual human studies are done for several years with natural estrogens in varying dosages,  their safety will not be known to their full extent. When ingested orally, these hormones are altered by the liver before they make it to the cells. Therefore, cell studies in a laboratory do not give us the full picture. Also, what if we find out someday that natural hormones stimulate cancers in certain tissues of the body more potently that the horse estrogens? At this time we don't have any long terms studies that compare bioidentical hormones to Premarin.

Other points to keep in mind:
How are we to know for sure whether compounding pharmacies are preparing the correct bioidentical hormones since there is little or no oversight?
How do we know the right dosages for these bioidentical hormones in terms of long term use? How many years should one take them? When should one stop using them?
How do we know which form of estrogen is best: estriol, estradiol, estrone, and in what proportions? How do we know whether slow steady release / absorption of these hormones is better or worse that a quick absorption with a high peak and low valley?
How do we know which is better, oral or topical hormone use?
How do we know whether saliva testing is reliable? How is one to know the right hormone dosage to use based on saliva testing or blood testing? There is little evidence that a blood level or saliva level of a hormone can predict exactly the actual hormone amount a woman needs to take. The dosage of these hormones is most likely best managed through symptom relief of hot flashes, mood swings, sleep problems, and other symptoms rather than relying on blood or saliva levels.
Could natural progesterone have a protective effect on breast cancer but potentially cause other health issues such as an increased risk for heart rhythm disturbances?
If you're considering starting hormone treatments to ease the hot and bothersome symptoms of menopause, keep in mind that you could suffer even more if you ever stop the therapy. Findings of a study, part of the large-scale Women's Health Initiative (WHI), may give postmenopausal women pause before starting replacement of their body's declining levels of estrogen. Evidence seems to suggest that 25 percent or more of women who start hormones might find it very difficult to stop them -- ever. Menopause, online May 24, 2010.

My opinion as of 2018
The bottom line is that every woman has to decide for herself whether the benefits of hormone use, in terms of menopause symptom relief and potential reduction of osteoporosis or treating other medical issues, outweighs the potential risks for cancer, heart attack, stroke, or other serious conditions from HRT use. Does the use of hormone replacement increase or decrease mortality? The answers are not yet in.
   Keep in mind that there is a physiological reason why hormone levels drop with age. The human body was not meant to be exposed to high levels of certain hormones with aging. Therefore, any form of hormone replacement through pills, creams, or shots, and whether synthetic or bioidentical, is not something the human body is genetically adapted to. Humans have lived on this planet for a long, long time but it has been only in the last few decades that doctors started prescribing hormone replacement therapy to such a large number of women. If, a decade or two from now, research shows bioidentical hormone use to be safe, I will wholeheartedly promote their use. Until then, women who are using these hormones, particularly in high dosages and for prolonged periods, are taking a gamble. If natural hormone replacement is the only solution to reducing your menopausal symptoms or taking care of other health issues you have, use the least dosage that works and for the shortest period of time. Exercise, weight training, calcium and vitamin D are a few good options in reducing the risk for osteoporosis. The risk for heart disease, stroke, and mental decline can be reduced through diet, exercise, low stress, yoga, deep sleep, and by taking certain natural herbs and supplements.
   I want to emphasize that I am not in favor nor am I against the use of hormone replacement therapy. I just want women to be aware of all the benefits and risks and make an informed decision. The quality of life of many women has improved through HRT, whether synthetic or bioidentical, while other women have discovered the use of hormones has caused more problems than benefits. I support a woman's decision, no matter what, as long as she is informed and knows all the options, benefits and risks.

Menopause hormone replacement therapy
Did you hear the news that fewer women are being diagnosed with breast cancer? Estrogen and progesterone hormone use plummeted after a 2002 study found that hormone replacement therapy after menopause raised the risk of breast cancer, heart disease and other problems. Before that, the regimen was believed to prevent many of these conditions, and doctors prescribed them as little fountains of youth. The decline in new breast cancer cases in 2003 is thought to have come because millions of postmenopausal women stopped hormone replacement therapy in 2002. There appeared to be a 7 percent drop in breast cancer incidence between 2002 and 2003 and most researchers believe it is related to the discontinuation of the hormones.
   My comments: Many of you already know that the estrogen most commonly prescribed for women as hormone replacement therapy after menopause is Premarin derived from the urine of pregnant mares (horses). The progesterone prescribed to women by doctors most often is a synthetic progestin, not actual progesterone made by the body. Some people claim that the use of natural bioidentical hormones would not cause as many problems in women as the use of Premarin or progestins. However I have not seen any long term studies comparing the two regimens and for the time being I will assume that the risk for breast cancer in women with the use of bioidentical hormones is similar until proven otherwise. Lately Suzanne Somers, the TV actress, has been heavily - and somewhat irresponsibly -  promoting her book suggesting women use bioidentical hormones to improve their health. I think this is a better option than artificial estrogens and progestins, but there is no evidence that they are safer and before you take high doses of these hormones keep in mind that it is a possibility that future research may show misuse of these bioidentical hormones carries serious risks. There are two natural hormones -- DHEA and pregnenolone -- available over the counter. Be cautious with their use since they can have serious side effects. Hormone supplements are not to be toyed with but be treated with respect, even if they are available without a prescription.

Hormone replacement therapy side effects, danger, caution and risk
Tumors in patients who use hormone replacement therapy are larger and more likely to spread beyond the breast compared with those who do not use HRT. Pro and cons of hormone replacement therapy continue to be debated, however there now appears to be more cons than pros. Research scientists at the Northern California Cancer Center and Kaiser Permanente's Division of Research have found significant reductions in both the use of hormone replacement therapy and the incidence of breast cancer in California in the years following the release of the 2002 Women's Health Initiative (WHI) trial results. Previous studies have shown that long-term use of hormone replacement therapy is linked to increased risk of breast cancer. For example, the WHI randomized trial and other studies discovered that estrogen plus progestin hormone therapy use increased a woman's risk of breast cancer. This new analysis, the first to use the most recent 2004 California Cancer Registry data, supports the theory that women who discontinue hormone replacement therapy use may reduce their chances of being diagnosed with breast cancer. "Hormone therapy use dropped 68 percent between 2001 and 2003, and shortly thereafter we saw breast cancer rates drop by 10 to 11 percent. This drop was sustained in 2004, which tells us that the decline wasn't just a fluke," notes Dr. Christina A. Clarke, the Northern California Cancer Center scientist who led the study. In the current study, researchers examined yearly prevalence of hormone therapy use and breast cancer incidence from 1994 to 2003 for women ages 50 to 74 in Kaiser Permanente's Northern California Region and in the 2004 California Cancer Registry. They found consistent evidence of corresponding trends in decline in both hormone therapy use and breast cancer incidence.

Review of WHI study by Lou Mancano, M.D.
Risks: In the Women's Health Initiative, combined estrogen-progestin therapy was associated with a significant increase in coronary events. CHD included nonfatal myocardial infarction and death due to CHD. There were 6 additional coronary events per 10,000 person-years on estrogen and progesterone and no additonal coronary events for estrogen alone. Data from Manson, JE, Hsia, J, Johnson, KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349:523. There were 8 additional breast cancers per 10,000 person-years on estrogen and progesterone. There were 18 additional thromboembolic events per 10,000 person-years on estrogen and progesterone.
Benefits: In the Women's Health Initiative, combined estrogen-progestin replacement therapy was associated with significant reduction in hip fracture (5 fewer hip fractures per 10,000 person-years, HR 0.7, unadjusted 95 percent CI 0.4 to 1.0). Data from Risks and benefits of estrogen and progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002. HRT seemed to protect against Colon Cancer with 6 fewer cancers per 10,000 person-years. Lou Mancano, M.D. 2009.

After hysterectomy hormone replacement therapy benefit
After a hysterectomy and/or bilateral ovariectomy, many women will experience hot flashes and lack of libido or sex drive, loss of bone mass, deterioration of the urinary and genital tissues. For women who undergo a hysterectomy and/or bilateral ovariectomy the effect of estrogen and progesterone deficiency is profound. Hormone replacement therapy benefit for a woman include stronger bones thus reducing the risk for osteoporosis, and improvement in sexual energy.

Male hormone replacement therapy HRT - hormone replacement therapy for man
The use of hormone replacement therapy in men is controversial. Levels of DHEA and testosterone drop as we age, but there is no proof as of now that hormone replacement therapy with testosterone or DHEA prolongs life span. It may be possible to enhance quality of life along with libido and vitality by taking certain hormones, but if you plan to do so, use very, very, low amounts of hormones and take frequent breaks.

Q. I have been a fan for many years and appreciate your insights into supplements and various nutritional therapies. I am 67 years old, and have recently become interested in DHEA and Pregnenolone, but am extremely frustrated in my search for protocols for taking the two together. I have seen articles recommending morning and evening, with food and without - very confusing. And have not found anything specifying on the best way to use both together. Can you advise on best ways to take both, whether they can be taken simultaneously or should be spaced apart. Whether divided doses throughout the day. Better with food or on an empty stomach, or sublingually? And do any other supplements help to optimize their effects?
   A. The reason there are no such protocol is because so little research is available regarding each one, and even less so together. The most practical approach is to take one or the other or both in the morning with or without food, but to keep the dosages extremely low, for a total of less than 10 mg together, and a couple of days off a week.

Drug for hormone replacement therapy
The medicines used for hormone replacement therapy are hormones, not drugs.

Questions
Q. First let me say how much I have enjoy reading your postings and information on your websites. I have subscribed to your newsletters and look forward to receiving those regularly. I am constantly learning!! I am a 51 year old healthy female who had been taking synthetic hormones in the form of an estradiol patch (highest dose available for 1.5 years) and a Prometrium tablet for about 1 year until November 2006. I was not happy with this form of female hormone replacement therapy. Yes, it did resolve the hot flashes and the mood swings were manageable but I didn't like taking synthetic hormones. I was introduced to your website and pregnenolone while searching for other options. I started taking about 2.5 mg of pregnenolone orally (from a 15mg capsule). I am experiencing lower back pain and leg cramps similar to the cramps I had when I started a menstrual cycle. When I began taking the Prometrium (October 2005), my cycles stopped. I have had 3 since then and experienced spotting on occasion. Right now, I am experiencing hot flashes - day and night - and the cramping. I am prepared to do a saliva test to determine how my body is handling the stress hormones and what exactly is going on with my hormones. Should I be concerned about the leg cramps (which wake me up) and should I discontinue using the pregnenolone or increase the dose for the symptoms of menopause?
   A. This is a personal question that you need to discuss with your doctor regarding the best option in your case for optimal female hormone replacement therapy. Without knowing your full history, blood work, or doing a medical evaluation, we would not be able to provide accurate suggestions.

Q. Are you familiar with the French study on the use of bio identical hormones? It was published in a journal called Maturitas. It says tens of thousands of French women were studied who used bio identical hormones. The study claims that women who used the Bio identicals, had no elevated risks of cancer. I am on bioidentical hormones and I am researching any studies that show the safety of these hormones. I wondered what you thought of this French study.
   Could transdermal estradiol plus progesterone be a safer postmenopausal HRT? A review. Marc L’Hermitea, Tommaso Simoncinib, Sarah Fullera, Andrea Riccardo Genazzanib. Published online 22 August 2008.
   Hormone replacement therapy (HRT) in young postmenopausal women is a safe and effective tool to counteract climacteric symptoms and to prevent long-term degenerative diseases, such as osteoporotic fractures, cardiovascular disease, diabetes mellitus and possibly cognitive impairment. The different types of HRT offer to many extent comparable efficacies on symptoms control; however, the expert selection of specific compounds, doses or routes of administration can provide significant clinical advantages. This paper reviews the role of the non-oral route of administration of sex steroids in the clinical management of postmenopausal women. Non-orally administered estrogens, minimizing the hepatic induction of clotting factors and others proteins associated with the first-pass effect, are associated with potential advantages on the cardiovascular system. In particular, the risk of developing deep vein thrombosis or pulmonary thromboembolism is negligible in comparison to that associated with oral estrogens. In addition, recent indications suggest potential advantages for blood pressure control with non-oral estrogens. To the same extent, a growing literature suggests that the progestins used in association with estrogens may not be equivalent. Recent evidence indeed shows that natural progesterone displays a favorable action on the vessels and on the brain, while this might not be true for some synthetic progestins. Compelling indications also exist that differences might also be present for the risk of developing breast cancer, with recent trials indicating that the association of natural progesterone with estrogens confers less or even no risk of breast cancer as opposed to the use of other synthetic progestins. In conclusion, while all types of hormone replacement therapies are safe and effective and confer significant benefits in the long-term when initiated in young postmenopausal women, in specific clinical settings the choice of the transdermal route of administration of estrogens and the use of natural progesterone might offer significant benefits and added safety. Keywords: Micronized progesterone, Transdermal estrogens, MPA, Postmenopause-hormonal replacement therapy, Cardiovascular risk, Hypertension, Breast cancer, Venous thromboembolism.
   A. The first sentence of this review makes me suspect that the individuals who wrote this review do not have a balanced position. They say, "Hormone replacement therapy (HRT) in young postmenopausal women is a safe and effective tool...." Most scientists are not as cavalier as these doctors. It would take at least several 10 to 15 year long studies with bioidentical hormones, in oral and dermal forms, in various dosages, and in various combinations of estrogen and progesterone, to have a better understanding of their long term benefits and side effects. To my knowledge, these types of studies for these time periods have not yet been done as of 2009. When Premarin and progestins first became available decades ago for hormone replacement therapy, many doctors were assuring their patients that they were safe. It took several decades to find out that serious problems could occur. I do not know Marc L’Hermitea, Tommaso Simoncinib, Sarah Fullera, Andrea Riccardo Genazzanib and do not know if they have any affiliations with pharmaceutical companies that sell these hormones.

I am a 37-year-old female who has been successfully using natural progesterone cream for at least 11 years. You recommend "taking frequent breaks" from HRT. What do you mean by that? I always stop using the product just before my menses ( or when they begin, if they begin early), and the only prolonged break I ever took was probably 10 years ago for about 6 wks, at the end of which I felt like I was losing my mind. Thinking of quitting progesterone, even for a time, is frightening to me, since I dealt with severe mood swings and extreme insomnia. Progesterone has made life manageable. Still, I want to be open to what is healthiest for my body. Any helpful info will be greatly appreciated.
    Different people have different needs regarding any kind of supplement or hormone replacement therapy. As a general rule, due to the fact that excess hormone use may have long term health consequences, it is best to use the least amount of these hormones and as fewest days. Each person needs to find out for themselves what the right dosage and frequency of use would be for their unique needs.