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Testosterone Replacement Therapy  ·  Hormone Replacement Therapy

Turn on the TV and it won’t take long to see commercials featuring sprightly seniors playing pickleball, going on a sexy date, or hiking up a mountain. These ads reflect our changing relationship with aging: Many Americans have come to expect a sense of vitality, energy, and libido that lasts well into their postretirement years. And they’re increasingly turning to hormone replacement therapies to make it a reality.

Between 2003 and 2013, testosterone replacement therapy (TRT) use quadrupled in men between the ages of 18 and 45 and tripled among their older counterparts. Since then, the rise of telemedicine and direct-to-consumer advertising has continued to fuel the use of TRT. Meanwhile, the global hormone replacement therapy (HRT) market, valued in 2023 at approximately $24 billion, is projected to top $50 billion by 2033.

Concerns about aging and evolving attitudes about hormonal health have contributed significantly to this growth.

“There’s a growing understanding that sex hormones, such as testosterone, estrogen, and progesterone, play a vital role in our overall health,” says clinical pharmacist and nutritionist James LaValle, RPh, CCN, author of Cracking the Metabolic Code. “They’re not just sex hormones, although they’re made by our sex organs. They’re hormones that play an important role in the whole aging process.”

“They’re not just sex hormones, although they’re made by our sex organs. They’re hormones that play an important role in the whole aging process.”

In addition to sexual function and fertility, these hormones affect our hair, skin, muscle mass, metabolic health, gut function, blood-sugar levels, inflammation, and mitochondrial energy. Yet measuring sex hormones is often an afterthought among conventional medical providers.

“Hormones play an integral role in all these different processes, so to take them out of the aging equation or just dismiss them is really a disservice,” says integrative-medicine physician Tasneem Bhatia, MD, author of The Hormone Shift.

Still, changing hormone levels are a natural part of aging, and not everyone will need or want to supplement with exogenous (made outside of the body) hormones. There are side effects and risks to consider as well as other ways to mitigate aging’s more troublesome symptoms.

Some of these methods, such as eating a mostly whole-foods diet, exercising, repairing your gut, and regulating inflammation, offer salutary benefits that go beyond hormone health. Other approaches — such as herbal remedies, nutritional supplements, and acupuncture — can also deliver symptom relief. If used in combination with exogenous hormones, they may reduce the need for large hormone doses. (See “10 Essentials of Aging Well” where functional-medicine pioneer Frank Lipman, MD, offers simple strategies to improve how we age.)

This is where Sara Gottfried, MD, director of the precision medicine program at the Marcus Institute of Integrative Health at Thomas Jefferson University and author of The Hormone Cure, likes to begin. “I start with lifestyle changes when I’m treating a patient, and if they’re ineffective, I begin hormone therapy in people who are good candidates,” she says.

When appropriate, bioidentical hormones (more on that later) can be another alternative. But they also require close monitoring.

“It’s not like taking a dietary supplement,” LaValle notes. “[All supplemental hormones] are powerful drugs that need oversight by a healthcare professional who’s taken the time to really look at you and follows you regularly to watch for both positive and negative effects.”

These are some of the potential benefits and risks of supplemental testosterone, estrogen, and progesterone to offset the effects of aging — and a few alternatives worth exploring.

Testosterone Replacement Therapy

On a recent afternoon, my husband was relaxing in the sauna at the gym when he overheard a conversation among guys comparing their doses and delivery methods of testosterone. It appeared everyone in the sauna was taking it. When he opened his eyes, he was surprised to see the speakers ranged in age from their 20s to their 70s.

Perhaps this shouldn’t seem remarkable, as testosterone is synonymous with male virility — at least in the collective imagination. Everyone produces and uses testosterone, but generally speaking, it has a more influential role in the male body.

Testosterone is produced primarily in the testicles. It affects bone density, fat distribution, muscle strength and mass, facial and body hair, red-blood-cell production, libido, and sperm production.

Testosterone production peaks at about age 17 in most males, and levels remain high for the next 20 years or so. Most males — but not all — begin to experience a gradual decline in testosterone production at about age 40, an average loss of about 1 percent a year. (This differs from the sharp hormonal drop-off that occurs during menopause.)

By age 70, the average male’s testosterone production is 30 percent below its peak. But for at least 75 percent of older men, levels remain within the normal range — roughly between 300 and 1,000 nanograms per deciliter (ng/dl). The American Urological Association suggests a diagnosis of low testosterone only if levels fall below 300 ng/dl and clinical symptoms are present.

According to the Cleveland Clinic, symptoms of low testosterone (also known as hypogonadism) might include:

  1. Reduced sex drive
  2. Erectile dysfunction
  3. Loss of armpit and pubic hair
  4. Shrinking testicles
  5. Hot flashes
  6. Low sperm count
  7. Depressed mood
  8. Brain fog
  9. Increased body fat
  10. Enlarged male breast tissue (gynecomastia)
  11. Decreased endurance, muscle strength, and muscle mass

Causes of Low Testosterone

LaValle describes an “eight-lane highway” leading to low testosterone, with possible drivers including environmental toxins, poor nutrition, and stress hormones. Age isn’t always the main factor. “There are older men who have good testosterone levels and there are young men who, because of injury, overtraining, or stress, can have significantly lower testosterone,” he says.

“There are older men who have good testosterone levels and there are young men who, because of injury, overtraining, or stress, can have significantly lower testosterone.”

Studies have shown that athletes who undergo intense training regimens may have lower testosterone levels. Excess visceral fat is another risk. A recent meta-analysis encompassing 68 studies and nearly 20,000 men with obesity found that 43 percent of the participants had low testosterone.

“We like to divide testosterone deficiency into reversible and irreversible causes,” explains endocrinologist Bradley Anawalt, MD, the chief of medicine at University of Washington Medical Center in Seattle.

Irreversible causes of low testosterone might include issues with the pituitary gland or hypothalamus, injury to the testicles, or congenital testosterone deficiencies. Reversible causes include stress, overtraining, and being overweight — provided the underlying factors are addressed.

Weighing The Benefits and Risks of Testosterone Replacement Therapy

The benefits of TRT for people with irreversible causes of low testosterone are unambiguous, Anawalt says; they include improved sexual health, mood, muscle strength, bone density, and cognition. This is despite the therapy’s side effects, which may include acne, sleep apnea, hair loss, mood swings, and enlargement and tenderness of breast tissue.

When testosterone is low for other reasons, the benefits of TRT are less clear cut. “There’s a more controversial area of testosterone therapy, associated with aging, obesity, and poor overall health, which results in decreases in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) — the hormones that have a direct effect on testosterone production and the testicles.”

For men in this category, it’s worth trying diet and lifestyle adjustments before TRT. Importantly, supplemental testosterone turns off the body’s own production of the hormone. If you take it for more than a year and then stop, it takes time for the body to recover its ability to produce it. Some never regain that ability.

TRT comes with other risks. “When you take testosterone, you can lose a lot of sperm viability, motility, and quantity,” LaValle notes.

TRT comes with other risks. “When you take testosterone, you can lose a lot of sperm viability, motility, and quantity,” LaValle notes.

TRT can also lead to abnormal increases in red blood cells, raising the risk of blood clots, heart attack, or stroke. The risk is quite low among those with true testosterone deficiency who take testosterone to bring their levels up to the normal range, Anawalt says. “In that setting, there’s not a significant problem with heart disease or stroke.”

Supplemental testosterone can improve the symptoms of hypogonadism if someone is testosterone deficient, but TRT isn’t always helpful when symptoms, such as erectile dysfunction, are driven by other causes. “Men will search out testosterone for erectile dysfunction, but the reality is it doesn’t always fix it because [it could be] a microcirculation problem,” says LaValle.

If testosterone levels are normal, Gottfried notes, adding exogenous testosterone is unlikely to help build muscle or increase libido, stamina, or energy levels — and it can cause enlarged prostate, testicle shrinkage, and heart muscle damage.

Testosterone Replacement Therapy Alternatives

Ideally, TRT is “not the first choice in men who are in their 20s, 30s, or even 40s,” LaValle says, even if their testosterone levels are on the low side. “Rather, we want to look at how we can stimulate their brains to release luteinizing hormone, which tells the testicles to make testosterone.”

A drug called human chorionic gonadotropin (hCG) can boost that process; it can also increase fertility. It acts like LH, which stimulates the testicles to make testosterone. “You’re remapping your brain to get it back to what it should be doing in the first place,” LaValle says. It’s generally used as a short-term therapy. As testosterone production improves, users can taper off the drug.

Exercise is another excellent way to increase testosterone. A study published in Endocrine Connections found that a combination of preconditioning and high-intensity interval training increases bioavailable testosterone in sedentary men who were around 62, as well as in athletes in their mid-50s to mid-60s. Reducing alcohol intake and achieving a healthy weight can both help restore healthy testosterone levels. Weight management may also improve sexual function.

Certain herbs can inhibit the production of aromatase, an enzyme that converts testosterone into a form of estrogen: Inhibiting this conversion can naturally increase testosterone levels. A systematic review published in 2021 found that two herbs in particular — fenugreek-seed extracts and ashwagandha — may improve testosterone concentrations in men.

Testosterone Replacement Therapy Options

For those who opt for TRT, there is an array of delivery methods available, including injectable pellets, intramuscular and subcutaneous injections, and topicals. Bioidentical formulations (derived from plant sources such as yam or soy) may offer the opportunity for more fine-tuned dosing, as these formulas can be customized by your healthcare provider, though some experts advise caution because they’re not as well-regulated as synthetic hormones.

People taking any form of TRT need to be closely monitored by their healthcare providers. “The biggest thing is managing any potential side effects, such as ‘sticky blood’,” says LaValle. Sticky blood, which involves abnormally high levels of hemoglobin, is a precursor to blood clots. “Monitoring is an important piece.”

Hormone Replacement Therapy

After a period of reduced use following the much-contested Women’s Health Initiative (WHI) study in the 2000s, HRT is enjoying something of a resurgence among menopausal women.

The WHI study followed nearly 30,000 women between the ages of 50 and 79 who had enrolled in hormone trials in the 1990s. It found that those who took a combination of estrogen and progesterone experienced an increased risk of illness — including breast cancer. In the wake of these results, many women avoided HRT.

Critics of the study note that researchers only tracked postmenopausal women (with an average age of 63) using synthetic hormones. Today, providers have a greater understanding of how to customize HRT, using more modest doses of estrogen (ideally balanced with progesterone) to provide relief from menopausal symptoms. The availability of bioidentical hormones (chemically identical to those produced by the body) and an expanding array of delivery methods, including patches, gels, and inserts, have increased options as well.

Estrogen and Progesterone

During menopause and perimenopause (the years leading up to menopause), levels of both estrogen and progesterone begin to fluctuate and eventually decrease. This hormonal circus is responsible for the various physical and emotional symptoms associated with these years, such as hot flashes, night sweats, mood swings, vaginal dryness, and changes in menstrual patterns. The drop-off in estrogen is a hallmark of menopause and can cause various long-term health effects, including an increased risk of osteoporosis.

Gottfried notes that low estrogen is also common among women in their 20s, 30s, and 40s. “Subtle changes in the earlier years, such as night sweats before your period or dryness in the vagina, could be a tip-off that your estrogen levels are declining,” she says. Perimenopause typically starts in the early 40s, but earlier drops in estrogen can result from excessive exercise, restricted eating, exposure to toxins, or an autoimmune condition that affects the ovaries.

“When I’m seeking to balance estrogen levels that are not in the normal range, I don’t prescribe HRT before looking into a patient’s whole health history, diet, nutrition, lifestyle, stress levels, genetics, and history of trauma,” Gottfried says. “Only after a thorough investigation do I introduce exogenous hormones.”

Excess estrogen, or “estrogen dominance,” is another common pattern. In these cases, there’s more estrogen than the liver and gut can metabolize and excrete, so the hormone keeps recirculating. This can create serious long-term effects, including a greater risk of breast cancer.

All of this explains why regulating these hormones can be a challenge. “When I’m seeking to balance estrogen levels that are not in the normal range, I don’t prescribe HRT before looking into a patient’s whole health history, diet, nutrition, lifestyle, stress levels, genetics, and history of trauma,” Gottfried says. “Only after a thorough investigation do I introduce exogenous hormones.”

HRT typically involves a combination of estrogen and progesterone. Those who have had their uterus removed often receive estrogen only, but Bhatia thinks that may be a disservice.

“Progesterone reduces inflammation. It helps with sleep and plays a role in gut health,” she says. “My general recommendation is that women taking HRT are on both estrogen and progesterone because they both have a role in the overall arc of health.”

Weighing the Benefits and Risks Hormonal Replacement Therapy 

HRT can be a game-changer for women suffering from symptoms of menopause. “Hormone therapy is the most effective way to relieve vasomotor symptoms such as hot flashes and night sweats and has an efficacy of [up to] 90 percent versus placebo,” Gottfried says.

These symptoms aren’t just a nuisance, she adds. “They’re a biomarker of unstable blood vessels. Untreated vasomotor instability can impair the lining of blood vessels, leading to a greater risk of high blood pressure, cardiovascular disease, osteoporotic fracture, and depression.”

Evidence suggests that HRT significantly reduces all-cause mortality and cardiovascular disease when initiated in women under 60 years of age or who are at or near menopause, or both.

Timing is important. “When I prescribe hormone therapy, the age where I focus tends to be symptomatic women who are 45 to 55, or within five to 10 years of their final menstrual period,” Gottfried says. Beyond that window, risks can outweigh benefits.

And even within that age range, HRT might not be for everyone. “We each have a certain capacity to tolerate hormones — even our own. That’s due to our genetics, our lifestyle, our gut health, and other factors,” Bhatia explains.

She notes that she has a genetic marker called COMT, which affects her ability to metabolize estrogen. Women with COMT can easily end up with estrogen dominance, which comes with cancer risks. Those with a history or high risk of estrogen-dependent diseases like breast, ovarian, or endometrial cancer may be ineligible for HRT. The same goes for those with a history of blood clots, stroke, or heart disease, as HRT can increase the risk of thromboembolic events.

Those with a history or high risk of estrogen-dependent diseases like breast, ovarian, or endometrial cancer may be ineligible for HRT. The same goes for those with a history of blood clots, stroke, or heart disease, as HRT can increase the risk of thromboembolic events.

The risks for cognitive health are less clear. Multiple recent studies have suggested that HRT is associated with increased risk of dementia, even in women who received treatment at age 55 or younger. (It’s possible that this reflects an underlying predisposition in women with vasomotor symptoms like hot flashes and night sweats who would be more likely to seek out HRT.) Yet a recent study published by the University of Edinburgh found that introducing HRT during perimenopause correlated with better memory, cognition, and brain volume in postmenopausal women who carry the APOE-4 gene for Alzheimer’s.

Meanwhile, there are short-term side effects to consider. Some women experience breast tenderness, bloating, or mood swings. “These are all signs that hormones aren’t being metabolized correctly,” Bhatia says.

Bioidentical hormones can offer flexibility in countering some of these risks. Typically, hormones are prescribed in standardized doses and preparations, while bioidentical hormones are made in a compounding pharmacy, tailored for the individual. “Holistic, functional-medicine practitioners are inclined to customization of hormone levels,” Bhatia notes. “That’s the part that’s missing when we look at the general landscape around HRT.”

Different delivery methods for all supplemental hormones, including patches, creams, and sublingual tablets, also offer options for personalization. Vaginal estrogen and progesterone can help counter symptoms specific to this part of the body, without risking more systemic effects.

“There’s even topical estrogen you can use just on your face, or for hair loss,” Bhatia says. “And you can do really tiny doses, so you can get things really customized.”

Hormonal Replacement Therapy Alternatives

For anyone who prefers to avoid HRT, there are a range of diet and lifestyle tools to help ease the menopausal transition. Even for those who do pursue HRT, addressing issues like sleep, stress, alcohol use, nutrition, and gut health can ease symptoms and make treatment safer and more effective.

“Menopause is not just about hormones. You really want to spend some time dialing into your gut health, optimizing your liver health, and doing what you can from a muscle-building and movement standpoint,” Bhatia says. “Start with those things, and maybe even some herbs and supplements. Then if you’re still stuck, you can move on to HRT, and any hormones you take will behave in a much better way.”

Hormonal Replacement Therapy Complements

Bhatia finds that most menopausal women benefit from taking a methylated B vitamin complex as well as supplemental magnesium. “They really help the overall hormone profile,” she says.

Depending on the person, Bhatia may also recommend liver-supportive supplements such as N-acetylcysteine (NAC), glutathione, milk thistle, or calcium D-glucarate to promote detoxification and hormone metabolism.

Some of Gottfried’s favorite tools include:

  • Chasteberry for PMS, breast pain, menstrual irregularity, and infertility. It helps restore normal progesterone levels, which may help relieve symptoms of PMS, particularly in perimenopausal women. The average dose is 500 to 1,000 mg daily.
  • Maca for low mood, libido, and energy. “This herb has consistently been shown to increase estradiol, a type of estrogen, in menopausal women, and helps with insomnia, depression, memory, concentration, energy, hot flashes, and vaginal dryness, as well as improved bone density,” Gottfried says. Maca extract is available in capsule, liquid, or powder form. A common dose is 2,000 mg daily.
  • Vitamin E for vaginal dryness. Studies have shown that doses of 50 to 400 IU per day ease hot flashes and other low-estrogen symptoms. It may take four weeks of use to experience any effects.
  • Paced breathing (slow, deep breathing) for hot flashes. A Mayo Clinic study found that practicing paced breathing for 15 minutes twice a day reduces hot flashes.

Working with an integrative provider can help you chart a personalized course through your unique transition. They can also ensure supplemental hormones are as helpful as possible if you decide to pursue them.

“When you make the decision to do HRT, do it with the understanding that you’re signing up for a lot of constant monitoring, level checking, and imaging to make sure your body is tolerating it,” Bhatia says.

But don’t hesitate to explore your options, she advises. “Have an open mind and understand that the hormone toolbox is expanding.”

Mo Perry

Mo Perry is an Experience Life contributing editor.

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