Balancing Act

The ups and downs of hormone therapy

Dr. Habib Sadeghi
Oct 1, 2019 · 12 min read
Photo by Jeremy Thomas on Unsplash

For men, unless a chronic disease process or an exposure to toxins is involved, hormones remain at healthy levels while gradually declining over a lifetime.

Women, unfortunately, must face menopause, a more immediate and distinct decline in hormone levels over as little as 5–10 years.

Needless to say, this kind of rapid hormonal decline often creates symptoms that run the gamut from irritability to debilitating pain. It’s during this difficult time that some women may need hormone therapy (HT) to regain their peace of mind and quality of life.

I want to make it clear that I am not an advocate of HT for the purposes of extending youth or elevating levels to those of a 25-year-old.

The hormonal cascade requires a very delicate balance, and without the proper knowledge and precision of application, the introduction of exogenous hormones (those obtained from outside the body) can wreak havoc on one’s health.

Understanding Menopause

At any given time, there are about 50 million women in the U.S. going through the change of life we call menopause. (1) The biggest misconception about menopause is that women are in it for years. Actually, menopause is a woman’s last menstrual cycle or period. In Greek, the word menopause means: month (meno) and to cease (pausis). The average age of menopause for women is 51, after which time their ovulation cycle stops and they are considered postmenopausal.

It’s mainly the 5 to 10-year period leading up to menopause that gets the most press and causes all the trouble. It’s known as the perimenopausal period or perimenopause.

Here is where women experience widely varying degrees of a host of symptoms that include hot flashes, insomnia, mood swings, memory loss, depression, night sweats, loss of libido, joint pain, dry skin, fatigue, rapid heartbeat, frequent urination, concentration problems and weight gain. The severity of these symptoms often depends on a woman’s biological make up and the type of introduction she’s had into perimenopause.

If she’s in good health with no disease processes, a woman’s symptoms should begin in her 40s and progress naturally, which may or may not require HT.

Women with chronic or auto-immune disease and sometimes those who over-exercise can begin perimenopause earlier, usually in their mid-30s, resulting in a more intense experience that often requires HT. About 1% of women reach menopause before age 40. (2) Abrupt entries into menopause, through chemotherapy, radiation or hysterectomy, always cause severe symptoms that require HT.

Boom & Bust

As we know it today, HT didn’t come into existence until the late 1960s. When Dr. Robert Wilson’s book, Feminine Forever, was released in 1968, it became an instant sensation. In it, he describes how estrogen treatment can benefit a woman’s health and wellbeing through midlife. By the early 1970s, 28 million women were taking the estrogen drug, Premarin. The name was created from the origin of the estrogen, pregnant (pre), mare (mar), urine (in). Yes, that’s pregnant horse’s urine.

The HT revolution was short-lived when in 1975, the New England Journal of Medicine published research stating that women who took estrogen increased their risk for uterine cancer by 400%. After this made headlines, half of all American women quit taking Premarin immediately.

In the 1980s, it became clear that it was crucial that any woman taking estrogen, who also had a uterus, needed to take progesterone as well, to prevent hyperplasia, the thickening of the uterine lining that can lead to cancer. About the same time, the first synthetic progesterone drug, Provera, was released, as well as an estrogen/synthetic progesterone (progestin) combo called Prempro.

Clearing the Air

Over the years, there has been much confusion concerning HT and its relationship to increasing cardiovascular disease and cancer risk in women. Fortunately, there has been just as much research in the 48 years since HT began, and the air is finally beginning to clear. In short, HT can protect women from cardiovascular disease, and the only measurable risk for breast cancer lies with conventional HT, which is negligible at that.

Research published in the Journal of Women’s Health in 2006 shows that women who start HT (estrogen only) within a decade after menopause experience an 11%-30% reduction in heart attack risk.

The earlier HT is begun, the larger the benefit, with the youngest women receiving a 44% risk reduction. (3) A periodic review in the famous “Nurses’ Health Study” showed similar results that year. (4)

The real cardiovascular risk comes with women over age 60 with a history of cardiovascular disease who begin taking Prempro (estrogen and progestin) for the first time. These women show a legitimate increase in heart attacks, artery blockages and even gall bladder disease. It is not recommended that these women utilize HT. If, however, a healthy woman began HT earlier in life she can expect no problems as she passes into her 60s and beyond. (5)

With regard to breast cancer risk, a follow-up review of the Women’s Health Initiative (WHI) study in 2010 found that women taking Prempro had a higher rate of invasive breast cancer and mortality than the placebo group, (6) but this amounted to an increase of only 1.3 women in every 10,000.

To demonstrate how small this risk increase is, the percentage comparison would be 0.34% for the placebo group and 0.42% for the HT group — just eight one-hundredths of a percent. I’d also like to point out that although the media likes to keep American women’s attention focused on breast cancer, it’s not the number one cancer killer for women. That’s lung cancer.7

Conventional Hormone Options

Because , the most common form of conventional estrogen, is made from the urine of pregnant horses it can be problematic when introduced into the human body. Breaking it down, Premarin is estrone sulfate (>50%), equilin (15–25%) and equilenin.

These conjugated estrogens are called as such because they are not in the true molecular form of a woman’s own estrogen. Because of this, there is some concern over the equine (horse) estrogens in Premarin, particularly equilin and equilenin, and how the body metabolizes them. Research published in The Proceedings of the Society for Experimental Biology and Medicine, (8) and Chemical Research and Toxicology (9) shows that the body breaks down these foreign hormones into metabolites that have an even stronger estrogenic effect than the horse estrogens themselves. They create DNA damage in tissue that has been shown to be carcinogenic. (10) This could very well be the reason why studies show a very small increase in cancer risk in women on conventional HT. It should also be noted that because most prescription drugs like Premarin need to be heavily metabolized by the body, they raise insulin levels.

Real progesterone doesn’t have a long half-life. The pharmaceutical companies needed something that lasted much longer, so they created medroxyprogesterone acetate (MPA), also known as . It was created at the same time as the birth control pill, because in low, regular doses it prevents ovulation.

While estrogen has been shown to protect women against heart disease, synthetic progesterone or progestin (Provera), largely cancels out that benefit. When the WHI data was reviewed in 2010, women on Prempro did show an increase in myocardial infarctions and deaths from coronary artery disease, and blood clots in the first two years on HT. (11)

is a completely synthetic form of testosterone and has been around for nearly 50 years. As an anabolic steroid, it’s the most common type used by bodybuilders. It has a low bio-availability and is widely known for lowering HDL (good cholesterol), raising LDL (bad cholesterol) and damaging the liver. (12) Aside from these more serious issues, all conjugated and synthetic (conventional) hormones come with a host of side effects because they are not truly natural and will elicit a defensive response of some kind from the body.

Bio-identical Hormone Options

Bio-identical hormones are called as such because they are identical in molecular structure to the estrogen, progesterone and testosterone found in the human body. They are the exact same hormones the body uses, making their bio-availability very high and side effects virtually non-existent. Identical means they are an exact match, unlike the label of “natural,” which can be used to include many substances that might be from nature but are foreign to the human body.

Plants have hormonal properties just like humans, and in the 1930s, it was discovered that a plant steroid, diosgenin, found in yams could easily be converted into an exact match for human progesterone using only heat and pressure, no chemicals. Bio-identical testosterone also comes from yams.

In the same way, bio-identical estrogen is derived from soybeans. After the conversion process, none of the phyto (plant-based) estrogen properties remain in place. After conversion, it’s not similar to human estrogen; it’s identical. The plant-based estrogen structure no longer exists.

Myth Busting

Bio-identical hormones are the exact substances that the body creates, so unlike conventional hormones, they cannot be patented. Big pharma can’t make any money off of them. That’s why all the large longitudinal studies have always focused on synthetic and conventional hormones like Premarin and Prempro. It’s also the reason why drug companies like to spread misinformation about bio-identical hormones.

The biggest misconception they perpetuate is that bio-identical hormones are not FDA regulated. Regulation simply means that the FDA guarantees their purity and efficacy and standardizes the dosages. Bio-identical hormones are not FDA regulated because they come in individualized not standardized dosages, which maximizes their effectiveness.

It is important to understand however, that all bio-identical hormone ingredients are FDA approved for use. Bio-identical hormones are also provided by compounding pharmacies that follow the same state regulations as any other pharmacy. In addition to those safety measures, the Pharmacy Compounding Accreditation Board (PCAB) applies an additional set of stringent standards that compounding pharmacies must meet.

Supporters of conjugated and synthetic hormones like to claim that because bio-identical hormone prescriptions are formulated by hand, the levels of ingredients aren’t consistent from one prescription to another, altering their effectiveness.

They liken compounding to cooking, putting in a pinch of this and a dash of that with no real measurement of any ingredient. This is absurd. With a doctor’s order, a compounding pharmacist, using industry-approved measuring instruments, is able to raise or lower the amount of individual hormones to give a woman the ideal combination that works specifically for her. This frees women from being locked into standardized doses that may either be too much or too little to be appropriately effective. With hormones, very small amounts make very big differences, and accuracy requires flexibility in dosing.

It’s also common for detractors to point out that the American Medical Association (AMA) doesn’t endorse bio-identical hormones because of a lack of research. That’s because nearly all research studies are paid for by the pharmaceutical corporations that want to promote their products. Even the WHI, which used Premarin and Prempro, was partially funded by Wyeth-Ayerst, the company that makes Premarin. Who’s going to fund a national study on bio-identical hormones that can’t be patented, and from which no one can profit?

Fortunately, for over 40 years, women have taken bio-identical hormones without a problem. In addition to decades of anecdotal success, two recent independent studies on bio-identical hormones are proving what we’ve always known.

Reassuring Results

The Early versus Late Intervention Trial with Estradiol (ELITE) began in 2004 and released its results in 2014. The study, sponsored by the National Institute on Aging and performed at the Keck School of Medicine at the University of Southern California (USC), examined whether bio-identical estradiol slowed the progression of atherosclerosis in women. Test subjects without a uterus took only estradiol while those with a uterus also took bio-identical progesterone. Accumulation in the carotid artery was examined by ultrasound.

Results showed that bio-identical HT did slow the progression of atherosclerosis in women, particularly for those in the early stages of menopause. Older women who were further past menopause, while experiencing no negative effects, did not receive the same benefit. This seems to fit with other findings that show women receive protection against cardiovascular and other diseases from HT the earlier they begin. Hormones are about timing.

The Kronos Early Estrogen Prevention Study (KEEPS) was conducted by the Kronos Longevity Research Institute in Phoenix, AZ. The goal of the double blind, randomized, controlled study was to discover whether conjugated or bio-identical estrogen decreased the risk of heart disease in women if started within a few years after menopause.

Over 720 women between the ages of 42 and 58 who were within three years of menopause were divided into three groups. The first group took oral Premarin (0.45mg/day), a dose much lower than used during the WHI (0.625mg/day). The second group took bio-identical estradiol via transdermal patch (50ug/day). Both groups were given bio-identical progesterone. The third group was placebo.

Results released in 2012 showed that neither Premarin nor bio-estradiol had any negative effects on blood pressure. It seems probable that the benefit for the Premarin group was the result of a much lower dose than was given during the WHI, as well as help from the bio-progesterone. The majority of studies have shown Premarin with synthetic progestin does pose some risk of heart attack and stroke.

Premarin increased HDL and lowered LDL, but also increased triglycerides. Bio-estradiol had no positive or negative effects on cholesterol, but it did improve insulin sensitivity (reduced insulin resistance). At these doses, neither Premarin nor bio-estradiol had any impact either way on atherosclerosis. Both relieved symptoms and increased bone density while neither group experienced any major health crisis during the study. (14)

It comes as no surprise that during the tests, bio-estradiol had zero negative effects. In addition to relieving menopause symptoms and increasing bone density, it improved insulin sensitivity. This means that it’s protecting women against all the diseases that are connected to insulin resistance, a benefit Premarin doesn’t provide. This is most certainly due to its bio-identical and easily metabolized structure. The fact that Premain raised triglycerides is a concern and needs more study.

Women have been taking both conventional and bio-identical hormones for nearly half a century now without a major health crisis. This is what we know for sure. Women starting HT earlier, within five years of menopause, receive the greatest benefits and disease protection.

HT should never be started for the first time after age 60. That’s when real problems occur. Women with a uterus taking estrogen must also take progesterone to prevent thickening of the uterine lining. Tests also repeatedly show small but viable risks for cardiovascular disease and cancer when using conventional estrogen (Premarin), especially in conjunction with synthetic progestin (Provera/Prempro).

Because bio-identical hormones have shown no detrimental health effects whatsoever in testing, or over the last 50 years, it’s no surprise that I recommend them to my patients when needed. Besides, what could be a better replacement for your own hormones than your own hormones?

Hormones have a variety of delivery systems including capsules, sublingual pills, patches, creams and gels. Each woman will have her preference based on how they work for her.

Bio-identical progesterone must be taken orally because it’s not absorbed well by transdermal methods. When you begin and how long you’re on HT is between you and your doctor. My recommendation is that levels remain light, just enough to alleviate symptoms. The goal isn’t to return to the energy level of your 20s. We must honor the natural progression of life, while at the same time using the tools we have to give us the best quality of life at the time of life we’re already in.

[1] University of Maryland Medical Center, Complementary and Alternative Medicine Guide, menopause, introduction:

[2] Northrup, C. (2012). The Wisdom of Menopause: Creating physical and emotional health during the change. (p. 120). New York: Bantam books.

[3] Grodstein F, Manson J, and Stampfer M. Hormone therapy and coronary heart disease: The role of time since menopause and age at hormone initiation. Journal of Womens Health. 2006 Jan-Feb; 15(1):35–44.

[4] Grodstein F, Manson JE, Colditz GA, Willett WC, Speizer FE, and Stampfer MJ. A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Ann Internal Med. 2000 Dec; 113:933–941.

[5] Hulley, S et al. (1998). Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Journal of the American Medical Association. , 280(7), 605–613.

[6] Chlebowski R, et al. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. Journal of the American Medical Association. 2010; 304(15):1684–1692.

[7] U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2010 Incidence and Mortality Web-based Report. Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2013. Available at:

[8] Bhavanni, B. (1998). Pharmacokinetics and pharmacodynamics of conjugated equine estrogens: chemistry and metabolism. The Proceedings of the Society for Experimental Biology and Medicine. , 217(1), 6–16.

[9] Shen, L et al. (1998). Alkylation of 2‘-deoxynucleosides and DNA by the Premarin metabolite 4-hydroxyequilenin semiquinone radical. Chemical Research in Toxicology. , 11(2), 94–101.

[10] Zhang, F et al. (1999). The major metabolite of equilin, 4-hydroxyequilin, autoxidizes to an o-quinone which isomerizes to the potent cytotoxin 4-hydroxyequilenin-o-quinone. Chemical Research in Toxicology. , 12(2), 204–213.

[11] Hulley, S et al. (1998). Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Journal of the American Medical Association. , 280(7), 605–613.

[12] Methyltestosterone. Retrieved from Http://www. Steroid. Com/methyltestosterone. Php#.

[13] Hodis HN, Mack WJ, Shoupe D, et al. Testing the menopausal hormone therapy timing hypothesis: the Early Vs Late Intervention Trial with Estradiol. Circulation. 2014;130:A13283.

[14] Tsagkas, V. Hormone therapy has many favorable effects in newly menopausal women: Initial findings of the Kronos early estrogen prevention study (KEEPS).

Dr. Habib Sadeghi

Written by

Dr. Habib Sadeghi is the founder of Be Hive of Healing, an integrative medical center based in Los Angeles, and author of The Clarity Cleanse.

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