The change was hard for Jane Dales. A British expat living in Spain, she was 52 years old when she felt the full force of her haywire hormones in menopause. At night she tossed and turned, her mood took tumultuous swings, and she had frequent hot flashes. Her outlook had darkened, too. "I had no joy in anything," Jane recalls. "I am always a very positive person, but positivity had gone out the window. I was putting on weight; my skin was getting thin and like crêpe paper. My hair was falling out in handfuls. I just felt like I wanted to crawl under a rock and hide. I was totally desperate."
About 30 million women in the US alone are in that phase of life, usually somewhere between ages 45 and 55, when the hallmark of their reproductive capacity, menstruation, gradually winds down and ceases. Estrogen, the hormone that makes fertility possible, nurturing not just the breasts and uterus but also the brain, bones, liver, heart and other tissues, and performing many functions like fat and glucose metabolism, slowly declines, as do other hormones like progesterone.
The process can take years and sometimes involves hormone ups and downs that produce a host of symptoms including hot flashes, vaginal dryness, poor sleep, decreased libido and weight gain around the middle. Frequently, it comes at a time of life when other things are changing too—empty nests, aging parents and realigning relationships.
Some women sail into menopause and hardly notice the change. For others like Jane it demands their attention. Most of the millions of women in perimenopause—the long phase before "true" menopause when menstruation has ceased for a full 12 months and beyond—experience some symptoms.
If they approach their doctor, they may be prescribed standard hormone replacement therapy (HRT)—usually a combination of estrogen and progestogen, chemical copies of the two most active hormones in their bodies—which has a long, conflicting history of research findings, the latest of which support the bad news.
Breast cancer risk
A new large-scale analysis of data from more than half a million women, published in the prestigious medical journal The Lancet, has confirmed that taking pharmaceutical hormones for menopause symptoms increases breast cancer risk. The higher the dose and the longer the women took the drugs, the greater the risk. What's more, their cancer risk stayed elevated for over a decade, even after they stopped taking the drugs.1
This study supports the results from the landmark 2002 Women's Health Initiative—involving more than 160,000 postmenopausal women—which showed that conventional HRT with estrogen and progestogens dramatically increased women's risk of strokes, dementia and breast cancer.2
The Women's Health Initiative was an HRT party-crasher. In the 18 months following its publication, HRT prescriptions in the US plummeted by half.
Nonetheless, women in menopause had heard for years that they needed to replace estrogen. "There was this medical argument that came from the pharmaceutical industry that women will disintegrate if they don't get the drugs," says Christiane Northrup, a retired obstetrician and gynecologist who has authored a number of best-selling books on menopause including The Wisdom of Menopause (Bantam Books, 2012) and Goddesses Never Age (Hay House, 2015).
Outside mainstream medicine was a huge smorgasbord of hormonal-balancing herbs, supplements and a growing industry of "bioidentical hormones" waiting to fill the gap.
HRT vs. BHRT
Millions of women first heard about bioidentical hormones from celebrity Suzanne Somers, who put "bioidentical" in the spotlight more than a decade ago with her series of books on the subject. "By replacing my hormones with bioidentical hormones, I got my life back," she raved to Oprah Winfrey in 2009. "I got my health back, I got my figure back, I got my happiness back. Everything in my life is better."
Bioidentical hormones, while not derived from human sources but from plants like soy and yams, are "identical" in molecular structure to human hormones. Like the correct piece in a puzzle, they are designed to fit perfectly into hormone receptors on human cells.
Non-bioidentical pharmaceutical concoctions don't match any receptor exactly. Their structure has been tweaked so they can be patented for profit (since natural substances cannot be patented).
However, to complicate matters, some modern pharmaceutical products are bioidentical, because the pharmaceutical companies are able to patent bioidentical products that are specially "compounded" to make a unique combination or delivery system, including pills, patches, creams, suppositories and even surgically implanted pellets that slowly release hormones.
Or take the case of Premarin, derived from horse urine, which is actually a bioidentical hormone—for horses. It matches the receptors for horse estrogen and is a close fit to the human receptor, but biologically much stronger. Premarin is "natural" in that it's from nature, but some would say it is unnatural for a woman to swallow it.
Champions of bioidentical hormones will often describe the differences as "natural" versus synthetic, but all the hormones are synthetic. Whether they're an exact hormone copy or not, they've been created entirely through processing in a lab.
Dr Michael Telford, former medical advisor to the company that produces Gestone, a bioidentical hormone created from the fibrous root sisal, explained to this magazine that the human body produces a basic steroid "skeleton" from which it creates all its hormones. This skeleton goes through a number of molecular changes, governed by enzymes in various organs, to transform into hormones like progesterone and estrogen.
Chemists making so-called "natural" hormones imitate this process, starting with a plant-derived molecule similar to this basic skeleton, then subjecting it to chemical reactions that yield an end product with the same molecular structure as what our bodies produce—but there is nothing natural about how they came to exist.
Drugs masked as supplements
Advocates of bioidentical hormone replacement (BHRT) say that most of the ill effects of HRT have been found with synthetic progestogens like medroxyprogesterone acetate, and that "natural" progesterone has a different risk profile.
They often cite studies such as a 2008 analysis of postmenopausal women, which found that invasive breast cancer risk was elevated among those taking estrogen and progestins but not among those taking estrogen and progesterone.3
However, the late Dr Ellen Grant, who participated in early trials of the Pill and HRT and became a vociferous critic of all supplemental hormones, "natural" or otherwise, said, "Both progesterone and Pill progestogens produce identical changes in endometrial cells, enzymes and blood vessels.
"Both relate to widespread systemic effects such as headaches and mood changes. Any differences are of degree and individual sensitivity, but not of kind."
She drew attention to research linking progesterone to cancer and birth defects4 and showing that progesterone skin gel, once absorbed by the body, can increase levels of the estrogen estradiol—high levels of which have been linked to endometrial cancer.5
Alarmingly, their "natural" label means that bioidentical progesterone products have avoided much of the scrutiny of their synthetic counterparts.
Critics of bioidentical custom compounding pharmacies say that BHRT preparations have slipped through a regulation loophole, so they don't undergo any of the monitoring and safety reporting required of drug companies.
"In the USA, it became an unregulated drug manufacturer industry in disguise, without proper control and making false claims and misleading advertisements" says a 2017 review of the subject.6
What this means is that these products are being used with virtually no oversight for quality control or side-effect risks.
Fountain of youth or medicalization?
Both old mainstream gynecology and new anti-aging medicine see hormones as an indispensable "fountain of life"—run dry. "Hormone replacement is no different than giving insulin to a diabetic or thyroid hormone to someone who is hypothyroid," says retired obstetrician and gynecologist Barbara Taylor in one of her popular "Menopause Taylor" videos on YouTube.
Specialists like Taylor cite research such as the Danish study of nearly 700,000 postmenopausal women that found topical estrogen may significantly lower women's heart attack risk.7 How, they ask, could the hormones that bathed your body for years, nourished your cells and kept your skin and arteries soft, be dangerous?
This philosophy underpins much of anti-aging medicine today. But others, like Christiane Northrup, see the menopause industry as "medicalizing" the natural aging process and failing to respect nature's design.
Just as doctors used to "treat" menopausal symptoms with hysterectomies and still flatten out the slightest aberration in a teenager's cycle with birth control to "normalize" them, perhaps 60-year-olds just aren't meant to have the hormone levels of 30-year-olds coursing through their veins, as the Women's Health Initiative and Lancet studies suggest.
Miracle or nightmare?
The experiences of women themselves reflect the conflicts in hormone therapy. Jane Dales, for example, started on custom-compounded BHRT eight months ago, after a battery of tests to rule out thyroid and adrenal dysfunction. "The change is astonishing," she enthuses. Even her hair grew back to its former "crowning glory."
But other women describe BHRT as a "nightmare" rather than a dream come true. "Everyone raves about bio hormones, but I found they made my symptoms much worse," one woman commented on a thread about side-effects. "It was a horrible and expensive experience for me. The doctor kept telling me to tough it out, but she was not in my body."
One woman started having delusional thoughts and panic attacks soon after starting bioidentical progesterone cream that were so severe she was hospitalized. A 35-year-old prescribed bioidentical progesterone cream stopped using it after14 days "when I started having panic attacks out of nowhere, crying spells, intrusive thoughts, inability to concentrate, difficulty sleeping, etc. . . I have been off for about nine days and still feel the effects."
Some women describe having to beg doctors to remove surgically implanted hormone pellets. "I pluck dark hairs from my moustache area daily," one woman complained about her bioidentical hormone implant. "I can't wait for this stuff to wear off."
Another woman who'd contacted this magazine went on to develop breast cancer after being told to use rub-on progesterone to prevent it, and was attempting to sue the American medical center that prescribed it to her.
The trouble with hormones
What can explain these disparate results? Getting the dose right is crucial with hormones, and overdosing is a real risk. Delivery system is important as well, and many practitioners using bioidentical hormones advise against taking them as a pill.
"If you swallow steroid hormones you will seriously distort their natural metabolism, " osteopathic physician and health advocate Joseph Mercola wrote on his website. "Only 10-15 percent will eventually reach the target tissues, and you will need to take an oral dose that is 500 percent higher than you need." What's left behind as metabolites in the liver can cause unwanted side-effects like those described by unhappy users.
Many women are drawn in by the claims of greater safety for hormone creams and gels that are applied to the skin—especially since these are not subject to FDA approval and marketed simply as "cosmetics." But there are dangers with creams, too, notes Mercola.
"I have learned that although progesterone cream is an enormously useful tool, it needs to be used very cautiously."
Over-the-counter products also have wildly varying concentrations. When one laboratory analyzed 19 different topical creams containing progesterone, for example, it found that the creams contained anything from less than 2 mg to 700 mg per ounce.8
Getting it right
Balancing hormones is a tricky art. These tiny molecules act as powerful signals to other players in the body, triggering cascades of action. "You have to get the right form of the hormone, the right dose, the right timing and the right delivery system," explained Jonathan Wright, an early pioneer of bioidentical therapy.
But the problem with this art, says Northrup, is that "women are getting the wrong stuff at the wrong dose, and they're not individualizing it."
Northrup recommends the Dutch 24-hour dried urine test for getting the most accurate picture of the state of fluctuating hormones. "Some women do beautifully on bioidentical hormones," she says, "while others have to quit. Some women do very well on herbal supplements that contain plant estrogens (phytoestrogens) and others find they don't work."
Northrup says she tried bioidentical estrogen and "it didn't do a thing for me." Yet she takes herbal remedies and offers maca root and Pueraria mirifica (see box, right) and has seen it help women "again and again."
And of course, some women don't need hormones. "There are so many ways to keep your brain and your body healthy, and we can't underestimate the lifestyle things," says Northrup. These include:
• A 'clean' unprocessed diet as free of sugars and excess carbohydrates as possible
• Adequate sunshine to make sufficient blood vitamin D levels for bone health
• Adequate sleep
• Meditation to relieve stress
• Magnesium to promote bone health
• Addressing underlying issues. Often, a woman's hormones are blamed for symptoms like low libido, for example, when there are many possible causes from unresolved issues in the relationship to unhealed trauma or exhaustion
London-based naturopath Robert Jacobs agrees that balancing hormones without addressing underlying lifestyle imbalances is fruitless. He recommends the Array 3 and 4 tests from Cyrex Labs to indicate immunological reactions to food ingredients. These can manifest as subtle allergies or autoimmune conditions that may mimic or worsen "hormonal" symptoms, says Jacobs.
Another issue is genetic differences in how we process hormones. "If you are going to use any hormones, you want to make sure the body is able to handle those hormones properly."
He uses the complete hormone and genetics profile tests from Genova Diagnostics to reveal "where the weak spots are and how the body is converting it." Women with a variation in their cytochrome p450 pathway, for example, will have compromised liver function when it comes to processing hormones.
"The first step is to unblock each of the pathways," says Jacobs. For these women, it's important that they take something—he uses chlorophyllin—to help their liver with hormones, be they bioidentical, which he doesn't prescribe, or phytoestrogens from plants like red clover, which he does.
Sometimes, the process of finding what works is trial and error. "At the end of the day," says Northrup, "women should heed their intuitions. You have to go with quality of life—how do you feel? And if you feel great, make sure you re-evaluate yourself at least once a year."
But before embarking on any "trials" of bioidentical hormones—even over-the-counter topicals—it's important to remember the risks involved and make sure you're working with an experienced practitioner.
The long and short of it is, a woman's response to hormones is highly individual and likely to change over time, and they aren't "natural" or as harmless as maintained. Furthermore, there are no long-term studies of their effects, they are unregulated, and there are safer herbal alternatives. Proceed with extreme caution.
"Natural hormones nearly killed me"
In 2004, Cathy Groves wrote to the British Medical Journal about her nightmare journey with progesterone cream. She'd had a terrible experience with the Pill, which affected her thyroid, and seeking to find an alternative to get her back to normal, she sought out a "natural" cream, following the manufacturer's instructions to use between 20-30 mg per day, split between morning and evening doses.
"When I first took the cream, beginning in May 2003, I felt great. In fact, I had more energy and ability to lose weight than I had in about five years. I didn't need near as much sleep, and found that I no longer struggled with depression," she wrote.
However, two months later, Cathy developed sharp pain in her legs, followed by a bruised and swollen lump and localized soreness in her calf, which continued to worsen.
"That ended up being the first of two episodes with venous blood clots in the six months I was on the cream. Little did I know that progesterone is heavily implicated in clotting disorders, much as the Pill is. Not one of my doctors ever made the connection between my blood clots and the progesterone."
Cathy's resting heart rate was going "through the roof," reaching 120 beats per minute. She also suffered crying spells, uncontrollable temper and bouts of nausea and vomiting.
"When I couldn't stop throwing up and couldn't eat and it had been three weeks—that was when I ran across the first doctor who said, "Well, if there's one thing I know that makes pregnant women sick as dogs, it's progesterone. I'd look there first." I quit the cream on October 26, 2003.
From there, it took six months for it to clear her body and for her to stop being sick.
"The symptoms during those six months of illness as I rebounded from the cream are almost too many to list, but they include: severe nausea and vomiting, gastrointestinal problems (marked heartburn, bouts of diarrhea, and bouts of constipation), uncontrollable shaking, acne and extremely oily skin, hirsutism, depression, anxiety, tingling/burning sensations on the back of my arms, neck and head, insomnia,hypersensitivity to medications and foods, hot flashes and serious withdrawal symptoms."
A TRULY NATURAL ALTERNATIVE
Many women don't want hormone replacement—bioidentical or otherwise—during menopause, but still want relief from some of its many associated symptoms from hot flashes to vaginal dryness.
Among the many herbal preparations and supplements on offer for that, Pueraria mirifica has unique estrogen-like properties.
P. mirifica is a woody, climbing plant found in Thailand, where it has been used for its anti-aging properties for centuries.
Local folk medicine suggests that both women and men can take a small piece of the plant's root, equivalent to about 5 mg/kg bodyweight, once a day at night to counter wrinkled skin, darken white hair and increase hair growth, alleviate cataracts in the eyes, help with memory loss, increase energy and vigor, provide more reflexive body movements, stimulate blood circulation and appetite and alleviate sleep disorders.
Many phytoestrogens that mimic human estrogen have been isolated from the plant's roots including the particularly potent miroestrol, which activates some estrogen receptors. A number of animal studies have confirmed the estrogenic activity of P. mirifica on the reproductive system, and it has been shown to influence reproductive function in both sexes, but particularly in females.1
In a double-blind randomized controlled study of 71 healthy postmenopausal women given a placebo or 20 mg, 30 mg or 50 mg of P. mirifica supplement for 24 weeks, the herb effectively decreased vaginal dryness.2
Another double-blind randomized controlled trial of postmenopausal women taking P. mirifica supplements with the same dosages and duration showed it improved their bone structure and slowed bone deterioration.3
Toxicity studies showed P. mirifica was safe at these doses, but be on the lookout for falsely labeled products, which have been reported. Vaginal creams with P. mirifica are available as well.
Concerns about progesterone cream
While some argue that progesterone creams are too weak to be effective, others contend that they harbor serious long-term risks. But there's one thing all the critics agree on: the dearth of medical evidence to support menopausal women using them.
Bioidentical progesterone cream was first developed by Dr John Lee, a general practitioner, in the 1970s, and marketed to menopausal women based mainly on anecdotal claims of "improved wellbeing" and recording of improved bone density among his patients.
There was no scientific evidence whatsoever to support this, but because they contained only "natural" progesterone, the creams never needed FDA approval.1
A number of studies have failed to find any beneficial effect of progesterone creams compared to placebo on menopause symptoms, including hot flashes, muscle aches, anxiety and decreased bone metabolism.2
Researchers have also warned that saliva tests, sometimes used by practitioners to convince patients the creams are working, mask the low levels of progesterone that reach the blood.3
And studies suggesting that these creams actually do affect symptoms leave even more cause for concern. Researchers from St. Luke's Hospitalin Pennsylvania found 20 mg of progesterone applied daily to the skin had no effect on bone density but did reduce "vasomotor symptoms" like hot flashes and night sweats.4
If this is really the case, as Dr Ellen Grant writes, it serves as "alarming evidence" that over-the-counter creams may suppress the immune system as strongly as steroids, which of course require careful medical monitoring due to their long-term dangers.
A 2005 study reported that an over-the-counter cream (Pro-Gest), applied at a dose of 40 mg twice daily had the equivalent effect of 200-mg oral progesterone capsules, suggesting again that the cream was far too powerful to be unregulated.5
Beyond the debate over whether short-term effects of hormone creams are too great or too small is the growing concern about how they accumulate.
Dr Mercola explains that his initial interest in the creams began in the early 1990s, when millions of women began using them due to their popularization in Dr Lee's book, What Your Doctor May Not Tell You About Menopause.
But he became "gradually disenchanted with them after I noticed that they typically worked wonderfully initially but then invariably stopped working. This is now known as 'dermal fatigue.'"
Any hormone applied to your skin will be absorbed by the fat tissue and accumulate there. "When one initially uses the cream, there aren't any problems as the fat stores are very low. But as time goes on, the cream accumulates and contributes to disruptions in your adrenal hormones such as DHEA, cortisol and testosterone.
"I found that many of the women who were on the cream have terribly elevated levels of this hormone," Mercola said.
"Progesterone is normally a cyclical hormone, and the body really needs to see a change in the concentration to affect a proper physiological response." If it is constantly leaking from tissue, this can't occur.
Once the negative effects begin, Mercola adds, it may take as long as two years for built-up excess progesterone (or other hormones) to wash out of the body.
It all boils down to Dr Grant's decades-long assertion that no hormone is a safe one unless the body produces it itself. As she wrote, "It is the same old hormone story—each disciple believes in special magic formulae for treating a physiological condition and chooses to disregard the evidence of much greater harms from using exogenous hormones."