Hormone Replacement Therapy - Yes or No?
Updated: Oct 27
The choice to use hormone replacement therapy (HRT) should be an individual one. It’s not an easy decision. HRT gets the job done. It works to relieve some of the symptoms of menopause. However, it has been associated with health risks since the beginning of its use. Personally, I’ve never been interested in HRT. I grew up in a home which used primarily natural healing. However, my interest is to provide all of the information necessary for a woman to make an informed decision. So, the following article outlines the history of HRT. At the end are some natural alternatives for managing menopausal symptoms and for raising estrogen naturally.
(Summary, for the details see below)
At the beginning of the 20th century, the FDA approved an estrogen product to treat hot flashes. The treatment became popular during the feminist movement of the 60s and the concept "feminine forever" was born. During the 70s, the associated risk of endometrial cancer was discovered. A low dose of estrogen combined with progesterone was introduced and received renewed interest. In 1988 prevention of osteoporosis was added to the list of official benefits and the term "feminine forever" was introduced, however the FDA started requiring proof of such benefits and in 1998 the Women's Health Initiative began. It was a large-scale study of 16,608 women using the combination estrogen therapy and estrogen alone. In 2002,due to the alarming incidence of cardiovascular disease and breast cancer, the study was terminated early. However, the use of estrogen alone and under specific circumstances has been proven less harmful more recently.
In the 20th century, the interest in menopause has been increasing, but it took a long time to realize the real impact of hormone depletion on women’s health. The clinical conditions associated with menopause were identified as “Hormone Deficiency Syndrome”, which included, besides hot flashes, other late onset chronic diseases such as osteoporosis, cardiovascular events, Alzheimer’s disease, and vaginal atrophy. At the beginning of the 20th century, the Food and Drug Administration (FDA) approved an estrogen product for the first time, Preamirin®, for the treatment of hot flashes.
The feminist movement in the 1960s changed women’s status and life expectancy, encouraging menopausal therapy, especially in European countries, with the concept of “feminine forever”. Wilson’s book, published in 1966 (“feminine forever”), became a bestseller, with its claim that “menopause is a hormone deficiency disease, curable and totally preventable, just take estrogen”. Hormone replacement therapy (HRT) was presented as a therapy that could allow women to free themselves from the malediction of estrogen loss and conserve their femininity.
In the 1970s, the finding that unopposed estrogen supplements were associated with an increased risk of endometrial cancer had a bad impact on HRT’s reputation.
Nevertheless, in the following years, researchers discovered that reducing the dosage of estrogen and combining it with progesterone could reduce the risk of endometrial cancer. Such combined therapy was recommended for women with an intact uterus, raising renewed enthusiasm for HRT treatment. The FDA initially approved HRT only for the treatment of hot flashes and not for the prevention of chronic conditions, but in 1988 the prevention of osteoporosis was included among the FDA-approved indications.
Furthermore, in the same years, numerous observational studies suggested that HRT had various benefits, not only with regard to the treatment of menopausal symptoms, but also in the prevention of chronic diseases. Thus, the idea switched from “feminine forever” to “healthy forever”. The use of HRT increased further, and the American College of Physicians developed the first guidelines for using HRT as a preventative therapy for the chronic diseases of postmenopausal women, even if experts raised some concern about the impact that progestin may have, particularly on the cardiovascular system.
On the basis of the claimed positive effect of HRT on cardiovascular health, the FDA required that this supposed HRT-induced cardiovascular benefit be confirmed by randomized clinical trials.
The first randomized clinical trial was a study of secondary prevention of cardiovascular disease, the Heart and Estrogen/Progestin Replacement Study (HERS). This study enrolled 2736 postmenopausal women with established coronary heart disease. Enrolled women were randomized to receive HRT or a placebo. No difference was found between the two groups after four years of follow-up, but in the HRT group, an increase of coronary events (nonfatal myocardial infarction or coronary heart disease (CHD) death) was found after one year. This induced increase declined in the subsequent years.
In 1998, the Women’s Health Initiative (WHI) was started, which was the largest randomized study to date that was aimed at evaluating the effect of HRT on the most common causes of death and disability in postmenopausal women, such as cardiovascular disease, cancer, and osteoporosis. 16,608 participants who had a uterus at that time were randomized and received a a combination of equine estrogen and progesterone, and 10,739 women without uteri were randomized and received estrogen or a placebo.
The first results of the WHI were published in 2002 after a follow-up period of 5.2 years. In the women with an intact uterus, an increased incidence of coronary heart disease and breast cancer was observed in conjunction with a reduction of osteoporotic fractures and colorectal cancer. Given these results, it seemed that the risks outweighed the benefits, and the trial was discontinued prior to completion. The data were largely disseminated to the media, creating panic among HRT users and forcing new guidance for doctors on prescribing HRT. The message was that HRT, with no specification of type and route of administration, was associated with more risks than benefits. No distinction was made between users and their age.
The trial with only estrogen (performed in hysterectomized women) continued, and the preliminary data were published in 2004. In addition, this trial was also stopped prematurely after 6.8 years of follow-up due to evidence of a small increased risk of ischemic stroke in the absence of other significant cardiovascular benefits.
Combination HRT Outcomes
Here are the the major clinical outcomes of the Women's Health Initiative study through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years.
Hot flashes can take a long-term toll on a woman’s health. The Study of Women’s Health Across the Nation (SWAN) showed that women with hot flashes had higher subclinical cardiovascular disease, including greater aortic calcification, poorer endothelial function, and higher intima media thickness, than did women without menopausal symptoms.
A connection between hormone replacement therapy and breast cancer has been shown. After the findings of the Women’s Health Initiative were released, HRT use declined, as did the rate of breast cancer. Clarke and colleagues were the first to publish data about the incidence of breast cancer between 2001 and 2003. The authors reported that after the WHI publication, the use of HRT in northern California declined by 68%, and at the same time, breast cancer incidence declined by 10%. A study performed in California between 2001 and 2004 similarly hypothesized that a decline in breast cancer incidence was linked to reduced HRT use. These data were in accordance with those observed in the Surveillance, Epidemiology, and End Results (SEER) study, which showed a 6.7% decrease in breast cancer incidence in 2003. Other western countries documented a reduction in breast cancer incidence after the reduced use of HRT. In Germany, breast cancer incidence declined by 8.8% annually from 2002 to 2005, with an almost 50% reduction in HRT use. In France, the breast cancer rate decreased by 14.7% from 2003 to 2007, with a reduction in HRT use from 32% to 11% between the years 2001 and 2007 . In Australia, a 6.7% decline in breast cancer incidence was observed in 2003, with a simultaneous 8% reduction in HRT use between 2001 and 2003 . In Canada, an 8% decreased incidence in breast cancer was observed every year from 2002 to 2004, with a 15% reduction in HRT use .
In 2018, a British study was conducted to assess the association between risk of venous thromboembolism and use of different types of hormone replacement therapy. 80,396 women aged 40-79 with a primary diagnosis of venous thromboembolism (blood clot in a vein) between 1998 and 2017, matched by age, general practice, and index date to 391,494 female controls. Overall, 5,795 (7.2%) women who had venous thromboembolism and 21,670 (5.5%) controls had been exposed to hormone replacement therapy within 90 days before the index date.
Of these two groups, 4,915 (85%) and 16,938 (78%) women used oral therapy, respectively, which was associated with a significantly increased risk of venous thromboembolism compared with no exposure for both oestrogen only preparations and combined preparations. Estradiol had a lower risk than equine oestrogen for oestrogen only preparations and combined preparations. Compared with no exposure, equine oestrogen with medroxyprogesterone acetate had the highest risk and estradiol with dydrogesterone had the lowest risk. Transdermal preparations were not associated with risk of venous thromboembolism, which was consistent for different regimens.
According to recent research, transdermal treatment was the safest type of traditional hormone replacement therapy when risk of blot clots in the veins was assessed. Transdermal treatment appears to be underused, with the overwhelming preference still for oral preparations. The latest recommendations regarding HRT made by the North American Menopause Society in 2022 include: For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is favorable for treatment of bothersome hot flashes and prevention of bone loss.
For women who initiate hormone therapy more than 10 years from menopause onset or who are aged older than 60 years, the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia. Longer durations of therapy should be for documented indications such as persistent hot flashes. For bothersome vaginal or sexual symptoms of menopause, not relieved with over-the-counter therapies, low-dose vaginal estrogen therapy or other therapies are recommended by the organization.
Natural Alternatives to HRT
There are two main types of natural HRT: Bioidentical HRT, and traditional natural HRT. Bioidentical hormone replacement therapy (BHRT) treats hormonal imbalances and depletion using synthetic hormones derived from plant estrogens. Traditional natural HRTs are supplements made from plants that may alleviate hormonal symptoms.
United States Food and Drug Administration (FDA)-approved BHRT: These medications are similar in safety and efficacy to conventional HRT medications. People who undergo not just BHRT — but any hormone therapy — can be at risk to develop blood clots and gallbladder disease. It can also increase your risk of stroke and breast cancer. The primary difference between BHR and HRT is the substances used to create them. BHRT hormones are plant-based. HRT Hormones are derived from pregnant horse urine and other substances.
Custom-compounded BHRT medications: A pharmacist mixes hormones according to a doctor’s prescription.
Traditional natural HRTs involve consuming plants or supplements containing compounds which alleviate hormonal symptoms. All plants contain phytochemicals. One group of phytochemicals, called phytoestrogens, mimics estrogen. When eaten, your body absorbs them during digestion and recognizes them as estrogen.
Foods containing high levels of these specific phytoestrogens include:
Nuts and Seeds, including almonds, flaxseeds, peanuts, sesame seeds, sunflower seeds
Soy and soy products, such as soybeans, tofu, miso soup, miso paste
Vegetables, particularly broccoli, Brussels sprouts, kale, onions, spinach, sprouts
Research suggests that phytoestrogens provide health benefits if you consume an average of 50 mg daily.
Vitamins and Minerals that Raise Estrogen
Some vitamins and minerals help your body produce estrogen and use it more effectively. To increase your estrogen levels, consider adding:
Boron, a mineral that helps your body absorb testosterone and estrogen
Vitamin B, which helps your body create and use estrogen
Vitamin D, which functions as a hormone in the body and helps with estrogen production
Vitamin E, because research shows vitamin E may help reduce hot flashes and insomnia.
Natural supplements which affect estrogen levels include:
Black Cohosh: People use this Native American herbal remedy to treat menopause symptoms associated with low estrogen. One small study shows it to be especially effective in treating hot flashes.
DHEA (dehydroepiandrosterone): A synthetic version of this naturally occurring hormone — available as pills, powders and topical treatments — can help produce other hormones such as testosterone and estrogen.
Red clover: This herbal supplement is rich in phytoestrogens. Research shows it is effective at alleviating hot flashes in menopausal women. Further study is needed to determine if red clover increases estrogen.
The decision whether to use hormone replacement therapy or not should be left to each woman to make for herself. One must consider the safety, availability and budget when choosing a remedy. However, no woman should suffer and there are plenty of safe, natural options available to try. Feel free to peruse this website to learn more about the various supplements, what they do, and how they affect the human body.