Over the past 30 to 40 years, books and articles have covered the subject of hormone replacement therapy (HRT). However, even with all of this attention on HRT, many women (and practitioners for that matter) are still confused or uninformed about their choices of hormonal therapy.
The scariest part of this is that they are often unaware of—or do not understand—the possible side effects and long-term risks of HRT, especially estrogen and progesterone replacement.
In this article, we’ll take a look at both estrogen and progesterone and what they do in your body, then discuss conventional HRT for estrogen and progesterone, their inherent dangers and the natural, safe and effective alternatives that abound.
Estrogen is the “queen bee” of the female sex hormones. As one of the two major female sex hormones, it is an especially important factor in health for women.
While we are accustomed to using the term estrogen, this term actually refers to several different types of estrogens made within the body. The three main types of estrogen produced within the body are estradiol, estrone and estriol.
Estradiol is the most potent form of estrogen. It is the primary type of estrogen produced by the ovaries during a woman’s reproductive years. Estrone is an intermediate-potency form of estrogen, 12 times weaker than estradiol. It is mainly produced within the fatty tissue of the body from precursor hormones made by the adrenal glands. Obviously, the more weight a woman carries, the more adrenal estrogen she is capable of making. The ovaries also produce small amounts of estrone after menopause, when production of estradiol ceases.
As these hormones pass through the liver, it is the liver’s job to detoxify and metabolize estradiol and estrone to a weaker form known as estriol. This weakest form of estrogen is 80 times weaker than estradiol.
When many women enter their menopausal years, they frequently experience symptoms such as vaginal dryness, more frequent bladder and vaginal infections and dryness of the skin. The long-term consequences of estrogen deficiency during the menopausal years, such as osteoporosis and an increased risk of heart attacks and strokes, do not initially produce symptoms. It is important that women check their risk of these conditions at the time of menopause with tests such as lipid panels and bone density studies, as well as routine blood counts and blood chemistry.
Many of these tests provide sensitive and very helpful indicators of early risk and are particularly important for women who do not want to use conventional hormone replacement therapy.
Progesterone is the yang to estrogen’s yin. While estrogen is a growth-stimulating and expansive hormone, progesterone tends to limit the growth of tissue, therefore having a more contractive effect on the body.
In fact, progesterone works in tandem with estrogen, in many cases acting to balance the effects of that hormone. For example, progesterone acts as a sedative on the nervous system, and high levels of progesterone can cause depression and fatigue. In contrast, estrogen has a stimulatory effect on the nervous system. High levels of estrogen can trigger anxiety, irritability and mood swings. Progesterone tends to elevate the blood sugar level, while estrogen lowers it. Thus, the healthy balance between these two female sex hormones is crucial.
Often a “silent partner,” progesterone is produced in the ovaries in women, with some production in the adrenals. During pregnancy, as the fetus matures, the placenta produces large amounts of progesterone (the name actually means “for gestation”). Low levels of progesterone can contribute to a number of health conditions and can negatively affect one’s outlook on life, energy level and emotions.
The “Gold Standard” is Fool’s Gold
For years, conventional physicians prescribed animal-based and synthetic HRT to women to help stave off hot flashes, night sweats, irritability and other menopausal symptoms. Additionally, the medical establishment has long believed that HRT—in the form of estrogen alone or estrogen combined with progestin—lowered postmenopausal women’s risk of heart disease and osteoporosis.
Available studies showed a 35 to 50 percent reduction in risk for CHD (coronary heart disease) among women taking HRT. The risk reduction was even higher among women known to have CHD before starting HRT.
One of the best-known studies of this time was the Postmenopausal Estrogen/Progestin Intervention (PEPI) trial, published in 1995 in the Journal of the American Medical Association.1 This study examined how HRT use impacted risk factors for CHD. In other words, the researchers simply monitored factors associated with increased and decreased risk of heart problems. The actual incidence of heart problems, such as heart attacks, was not monitored.
A total of 875 postmenopausal women received estrogen alone, estrogen and the progestin medroxyprogesterone (Provera), estrogen with micronized (oral) progesterone or a placebo. The authors noted improvements in blood lipid profiles among all women receiving hormones, including lower LDL (low density lipoprotein) levels and higher HDL (high density lipoprotein) levels. Based on these results, they endorsed the use of HRT to reduce CHD risk.
A few critics pointed to flaws in these early studies. All of the early studies were observational—meaning that the researchers simply observed and analyzed what happened to women who did or didn’t take HRT. Skeptics noted a strong possibility that the two groups of women weren’t matched with respect to their habits and lifestyles.
Worse yet, there was an extremely problematic finding from the study that was downplayed by the researchers. All of the women taking hormones experienced increases in their C-reactive protein levels. C-reactive protein, an indicator of inflammation, is now known to be a very strong predictor of future heart attacks, superior to LDL or HDL levels.
Of course, this finding and the concerns of alternative medicine physicians were largely ignored. The numbers were good and the medical profession believed, overall, that it had struck gold in the fight against postmenopausal heart disease. Soon, a prescription for HRT came to be considered the equivalent of a “heart disease insurance policy.”
Next came the randomized, placebo-controlled trials—far more scientifically rigorous than the older observational studies. Not surprisingly, these new studies started to show a very different outcome: Estrogen plus progestin doesn’t protect women against postmenopausal CHD. In fact, recent studies show that this therapy actually increases cardiac risk. This appears to be true not only for healthy women, but also for women who already have a history of CHD.
One of the largest randomized placebo-controlled trials of postmenopausal HRT to date is the Heart and Estrogen/Progestin Replacement Study (HERS) trial. A total of 2,763 postmenopausal women with a known history of heart disease received either estrogen plus medroxyprogesterone (Provera) or a placebo.2 The incidence of heart attacks and of other problems related to cardiac disease (such as bypass surgeries and hospitalizations for unstable angina or heart failure) was monitored. Data on other health problems were also collected.
The results clearly cast doubt on HRT. Researchers discovered that during the first year of use, women taking the hormones had significantly more heart attacks and other heart problems than those receiving the placebo. While the HRT group did eventually experience a decline in CHD risk, this did not occur until the third year of therapy. In fact, it wasn’t until an average of 4.1 years of use that women enjoyed a significantly reduced risk for heart disease in general or for specific heart problems.
Interestingly, the women receiving hormones did show improved blood lipid profiles, just like the women in the PEPI study. Yet those improvements were not associated with reduced risk of heart attack.
Then there’s the fact that the women in the HERS study who took HRT were found to have three times as many blockages of blood vessels by blood clots and a 40 percent increase in gallbladder disease, when compared to the women taking the placebo. Not exactly a ringing endorsement.
Based on these and other similar studies, influential organizations such as the American Heart Association and the American College of Cardiology began to issue warnings about starting HRT in postmenopausal women with a history of heart disease.
Similarly, the Food and Drug Administration (FDA) made drug manufacturers strengthen the warnings on package inserts and patient information sheets for HRT. They were now to read that women who take HRT are more likely to suffer from clots in their blood vessels than women not taking the drug.
Still, physicians continued to prescribe HRT. And then along came JAMA.
The Landmark JAMA-HRT Study
On July 17, 2002, the Journal of the American Medical Association (JAMA) reported on the findings from one part of the Women’s Health Initiative (WHI), an 8.5-year project funded by the National Institutes of Health.3 The WHI involved 161,809 postmenopausal women between the ages of 50 and 79, and outlined the benefits and risks of a variety of treatments designed to lower the incidences of several diseases, including heart disease, breast and colon cancer and fractures in postmenopausal women. Of this group, 16,608 women who were healthy and had an intact uterus participated in one part of the WHI, which tested the effectiveness of estrogen/progestin therapy.
According to the findings, women taking estrogen/progestin for five years or more had an increased risk for blood clots, coronary heart disease (CHD), strokes and breast cancer. The researchers concluded, “The results indicate that this regimen should not be initiated or continued for primary prevention of CHD.”
The data indicated that if 10,000 women took the drugs for a year and 10,000 did not, women in the first group would have eight more cases of invasive breast cancer, seven more heart attacks, eight more strokes and 18 more instances of blood clots.
In fact, researchers felt so strongly about the negative implications of long-term combined HRT, especially the unacceptably high risk for breast cancer, that they ended the study three years early! Participants were contacted and instructed to stop taking the drug—immediately.
As you can imagine, these findings turned the world of hormone replacement on its head. For alternative and complementary doctors, there was no surprise. For conventional physicians, the race was on to prove the study wrong.
They claimed that the Women’s Health Initiative (WHI) did, in fact, prove that women taking HRT enjoyed greater bone mass density and fewer fractures. The study found that taking combined estrogen/progestin for at least three years yielded a 3.7 percent increase in bone density and reduced hip fractures by 33 percent.
But that’s about all they could say. Subsequent studies have served to reinforce the deadly truth revealed by the July 2002 JAMA data. Continuing research from the WHI has shown that women who take combined estrogen/progestin replacement for at least five years have increased incidence of invasive breast cancer, as compared to women who don’t take HRT.4
They also found that women who took the combination for just one year had more abnormal mammograms than those who didn’t take the drugs. And taking estrogen didn’t help. Research indicated that taking estrogen for more than seven years also increases the risk of abnormal mammograms, and the need for subsequent follow-up.
Moreover, another follow-up WHI study found that women taking the conventional estrogen/progestin cocktail had an increased risk of ovarian cancer, and necessitated the need for 27 percent more endometrial biopsies, as compared to placebo.5
Clearly the research leaves little room for doubt about HRT and its negative effects on women’s health:
- It does not reduce a woman’s risk of heart disease. While it can improve HDL and LDL cholesterol levels, these improvements are not associated with fewer heart attacks or other heart problems.
- It increases a woman’s risk of heart attack, stroke and blood clots. In fact, it places healthy women and women with a history of cardiac disease at increased risk of heart attack within the first year or two of usage.
- It raises levels of C-reactive protein, an indicator of inflammation that is a strong predictor of a future heart attack.
- It increases the risk of invasive breast cancer.
- It increases risk of gallbladder disease by 40 percent.
While many physicians and researchers are still hoarding the “fool’s gold” known as HRT, complementary medicine is busily mining the mother lode of real gold—and women are taking notice.
Go Au Natural
When it comes to replacing and enhancing your own natural hormones, many complementary and alternative health practitioners turn to bioidentical hormones. Bioidentical hormones are molecularly identical to the hormones found in the human body. Moreover, they are produced in the laboratory from natural ingredients such as soy and wild yam. Since bioidentical hormones are biologically similar to the hormones your body produces, they do not appear to have the grave risks associated with conventional HRT.
The bioidentical estrogen most typically recommended is estriol. Of the three types of estrogen produced within your body, estriol is the weakest and least potent. More importantly, several research studies have found that it is as effective as the stronger, more potent estrogens for treating menopause symptoms.
One study published in the Journal of the American Medical Association found that estriol was particularly effective in treating vaginal atrophy, mood swings and hot flashes.6 Researchers selected 52 symptomatic, postmenopausal women and separated them into four groups, giving each group either 2 mg, 4 mg, 6 mg or 8 mg of estriol per day for six months.
On average, women in every group experienced a decrease in their menopausal symptoms after one month of treatment. Furthermore, in the groups with the three highest dosages, women who had ranked their symptoms as severe now felt that their symptoms were very mild.
Another study from Alternative Medicine Review found that estriol provides the protection of conventional HRT without the risks.7 Additionally, estriol was shown to ease menopausal symptoms, including hot flashes, insomnia, vaginal dryness, and urinary tract infections.
A study from Taiwan showed similar results. Researchers gave 20 menopausal patients, aged 44-62 years, 2 mg of estriol a day for two years.8 They found that estriol was significantly effective in easing menopausal symptoms (especially hot flashes and insomnia) in 86 percent of patients. Additionally, estriol did not cause proliferation of cells in the uterine lining. This is great news for women at high risk for endometrial cancer.
Natural progesterone has the same structure as the hormone the body produces. In contrast, while synthetic progesterone has somewhat the same function as the progesterone produced by the body—but many negative side effects—its structure differs slightly. In the United States, most prescriptions are for the synthetic form, called a progestin. The most common progestin is Provera, or medroxyprogesterone.
In addition to increased risk of breast cancer and heart disease, some women taking progestins experience debilitating side effects. These often include abnormal bleeding, fatigue, headaches, depression and mood changes, bloating, breast tenderness and enlargement, vaginal dryness and increased appetite. If any of these occur, physicians will often reduce the dosage.
Progestins can also cause more serious problems, such as an increased risk of heart disease. A double-blind, crossover study published in the Journal of the American College of Cardiology compared the effects of an estrogen/natural progesterone combination with estrogen/progestin combo in 18 postmenopausal women with known coronary artery disease.9 All the women were given estradiol for four weeks (1 mg/day for three weeks and 2 mg/day for the fourth week). Then, for an additional 12 days, the women continued to take 2 mg of estradiol each day, as well as natural progesterone gel (90 mg on alternate days). They then went another two weeks with just estradiol, then did an additional 12 days of estradiol but this time they added in 10 mg/day of progestin.
At the end of the study period, researchers found that 11 percent of the participants had to withdraw during the progestin phase, due to unstable angina. Additionally, when using the natural progesterone, women could exercise longer before experiencing heart palpitations. As such, researchers concluded, “These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration.”
One reason for this is that, unlike synthetic options, natural (or bioidentical) progesterone is produced from dioscorea, the active component of the Mexican wild yam. It can also be manufactured from soybeans. In either case, the resultant hormone has the same chemical structure and range of activity as the progesterone made by your body.
In addition to protecting your heart, natural progesterone can stimulate libido, help prevent and treat fibrocystic breast disease, regulate thyroid hormone activity, stabilize blood sugar levels and assist in normal blood clotting. Plus, natural progesterone is essential for the production of cortisone in the adrenal cortex and helps convert fat to energy.
Using Bioidentical Hormones
Estriol can be taken orally or used topically. If taken orally, a typical dosage is 2-4 mg daily, in capsule form. When used topically, many practitioners suggest applying one gram of the cream to your vagina every night for two to four weeks, then use twice a week for maintenance. Many women with vaginal or bladder symptoms may choose just to use the vaginal cream locally, limiting their total body exposure to estrogen.
In addition to estrogen alone, some researchers advocate the use of estriol in combination with estradiol (bi-estrogen or bivalent) or with estradiol and estrone (tri-estrogen or trivalent). In these combinations, the amount of estriol is far greater than the other forms of estrogen. In the case of trivalent estrogen, the ratios are usually 80 percent estriol and just 10 percent each estradiol and estrone. These combinations are also highly effective, and have also been shown to reduce menopausal symptoms, improve bone density and increase “good” high-density lipoprotein (HDL) cholesterol.
Estriol and all biochemically identical estrogen have to be prescribed by your physician.
Natural progesterone can be taken in oral micronized form or as a skin cream, rectal or vaginal suppository or sublingual drops. Other forms (such as Prometrium) must be prescribed by your physician. Be sure to check the label of any product that you buy to make sure it truly contains pharmaceutical-grade, natural progesterone in therapeutic doses.
In menopausal women, dosages of 100-200 mg of natural, oral progesterone (Prometrium) taken daily can be effective, although the dose can vary in either direction, which is why you need to work with your physician to be sure you are taking the appropriate dosage for you. Like the synthetic progestins, perimenopausal women should use oral micronized progesterone 10-13 days per month. If you are in menopause, most physicians recommend using it every day.
A range of progesterone creams, available without prescription, contain anywhere from less than 2 mg to more than 400 mg of the hormone per jar. The cream is applied to the skin and absorbed into the general circulation and reaches more body tissues than oral progesterone, which is first metabolized by the liver and converted into three different compounds.
A typical dosage of natural progesterone is 40 mg a day. A two-ounce jar should last for over one month. If you are perimenopausal, you should apply the cream from day 12 to day 26 of your menstrual cycle. If you are menopausal and not taking estrogen, you may use progesterone for two to three weeks each month, though some physicians do recommend daily use to avoid withdrawal bleeding.
The cream is used twice daily in ¼ to ½ teaspoon amounts, generally on rising in the morning and before going to bed at night. The cream can be applied to any area of the skin. Many women rub it into their chest, abdomen, arms or back. If the cream is absorbed rapidly (under two minutes), it means that the body needs a higher dose, and a slightly higher amount may be used. Blood or saliva testing of progesterone levels will help to determine if the level of supplemental progesterone you’re using is in the therapeutic range.
Note: Some reputed progesterone creams that contain wild yam extract contain only the precursor compound—diosgenin—and little to no progesterone. Also, progesterone delivered as a cream must suspend the hormone in a proper medium or it will not be effective. A cream containing mineral oil will not allow the progesterone to be absorbed properly. Some products have not stabilized the progesterone and, as a result, the hormone deteriorates over time. You can work with your health practitioner to find the best brand(s) for you.
Make the Transition Safely…and Naturally
The days of conventional medicine blindly leading women down the HRT path are over. From increased risk of blood clots and heart disease to more invasive and advanced stage breast cancer, science has shown that traditional hormone replacement has dangerous, and often lethal, repercussions.
The good news is there are gentle, safe and effective natural options. As we’ve seen with bioidentical hormones, Mother Nature has indeed provided a solution.
1. [No authors listed.] JAMA. 1995 Jan 18;273(3):199-208.
2. Hulley S, et al. JAMA. 1998;280(7):605-13.
3. Writing Group for the Women’s Health Initiative Investigators. JAMA. 2002;288:321-33.
4. Chlebowski RT, et al. JAMA. 2003 June 25:289(24):3243-53.
5. Anderson GL, et al. JAMA. 2003 Oct 1;290(13):1739-48.
6. Tzingounis VA, et al. JAMA. 1978 Apr 21;239(16):1638-41.
7. Head KA. Altern Med Review. 1998;3(2):101-13.
8. Yang TS, et al. Zhonghua Yi Xue Zhi (Taipei). 1995 May;55(5):386-91.
9. Rosano GM, et al. J Am Coll Cardiol. 2000 Dec;36(7):2154-9.