Bioidentical Hormones: Estrogen, Progesterone & Testosterone vs. Depression

The FDA is removing the boxed warning from hormone replacement therapy (HRT). What about the bioidentical hormones? Does the green light for HRT include the bioidentical hormones estrogen, progesterone and testosterone? What are the pros and cons of such therapy. You will learn how these hormones affect menopausal symptoms, mood and depression. What do women need to know before starting HRT, whether the hormones are synthetic or “natural”?

Bioidentical Hormones or HRT? Confusion About Breast Cancer:

Hormone replacement therapy has never been simple. For decades, women have been caught between fear and symptom relief–between hot flashes and scary headlines–while trying to make sense of contradictory data.

Women were told in the 1960s that hormone therapy would keep them looking “Feminine Forever.” That was the title of a book written by Robert A. Wilson, MD, in 1966.

Premarin (conjugated estrogens obtained from pregnant mares) became extremely popular in the mid-1970s. It was the most prescribed drug in America from the early 1990s until the early 2000s. Women were told that this form of estrogen would eliminate hot flashes and night sweats. In addition, many doctors told their female patients that Premarin would calm anxiety, slow the aging process, reduce the risk for osteoporosis and heart disease and keep wrinkles at bay.

Hormones and Breast Cancer Confusion:

An article in The Lancet Oncology published in 2012 reassured women that estrogen would not increase the risk for breast cancer and might even lower it. But research from the Nurses Health Study suggested that women who took both estrogen and progestin (Prempro for example) might have an increased risk of breast cancer. Needless to say, millions of women were confused by contradictory stories.

I won’t delve into the estrogen and breast cancer story in this article. If you are interested in this very complicated pharmacology, here is a recent article that explains why adding progestin to estrogen may increase the risk for breast cancer. In it, you will also find out why doctors add progestin to HRT. Here is the link:

“Estrogen and Breast Cancer: Yes – NO! – Maybe?”

Many women blamed adverse reactions linked to estrogen and/or progestin to drug company hormones. Estrogen from pregnant mares was considered dangerous for a variety of reasons, even though it is clearly “natural.”

Progestin from medroxyprogesterone acetate (MPA) was clearly not natural. It was included with estrogen to reduce the risk of uterine (endometrial) cancer. Many women assumed that any problems associated with a combination like PremPro would be eliminated by switching to bioidentical hormones. More about that shortly.

Why So Many Women Embrace Bioidentical Hormones:

Menopause is often portrayed as a minor nuisance: hot flashes that might last several months or a few years and some night sweats that could disrupt sleep temporarily. Eventually, everything is supposed to settle down.

The trouble with that narrative is that it does not work for millions of women. For far too many, menopause ushers in life-altering symptoms, including overwhelming depression. The following question from a reader—whose story mirrors that of countless women—illustrates just how devastating the hormonal transition can be, and how profoundly hormone treatment can change lives.

Bioidentical Hormones Plus Testosterone Overcame Depression:

Q. I went through a long, arduous menopause, over 10 years of pure hell. The killers weren’t the chills, night sweats or insomnia, though inadequate sleep does make you a little wonky. It was the major depression that almost did me in.

I finally consulted a physician who was a specialist in bioidentical hormone replacement. She did very thorough testing and balanced my female hormone levels. She also added a tiny dose of testosterone.

The results were nothing short of miraculous. I came out of the fog of depression almost overnight. That was after a decade of suffering. I had energy to exercise and dance again. And I could sleep.

Balancing out my hormones plus adding a dash of testosterone may have saved my sanity, if not my life.

A. Thank you for sharing such a compelling story. The FDA recently announced that it is removing the black box safety warnings on hormone therapy. FDA Commissioner Dr. Marty Makary has acknowledged what many women have been saying for years: menopausal symptoms can be not only disruptive but debilitating, including severe depression.

Yet one component of hormone therapy is rarely discussed—testosterone. Women produce this hormone too, although in much smaller amounts than men. And evidence is emerging that even a tiny dose may make a measurable difference for some women, particularly those struggling with mood disorders during menopause.

A study published in the British Journal of Psychiatry (June 16, 2025) reported that menopausal women receiving hormone therapy—including testosterone—experienced meaningful reductions in depression symptoms. Another comprehensive review in the journal Cureus (Aug. 28, 2024) found that testosterone may also help with vaginal dryness and can enhance sexual desire and satisfaction.

What Are Bioidentical Hormones?

The term bioidentical hormones refers to compounds with the same molecular structure as the hormones a woman’s body naturally produces. But many women remain confused by this terminology. And many healthcare providers have been skeptical about the entire concept.

The Food and Drug Administration has approved some bioidentical hormone replacement therapies that have been created by pharmaceutical companies. What it has not approved are custom-compounded bioidentical hormones made by compounding pharmacies. We have written about the FDA’s plan to eliminate natural desiccated thyroid extract in this article/podcast. It remains to be seen whether the FDA will take a similar approach to bioidentical hormones made in compounding pharmacies.

For women whose estrogen, progesterone, and testosterone levels have plummeted during menopause, restoring those hormones—carefully and individually—can sometimes produce dramatic changes in mood, energy, sleep and overall quality of life. This requires a healthcare professional who tests hormone levels very carefully and adjusts the dose of hormones accordingly.

Our reader’s experience is not unheard of. Severe perimenopausal depression is often biological, not psychological, and is linked to the sudden drop in ovarian hormones. For some women, antidepressants alone offer little relief because the underlying issue is hormonal imbalance, not neurotransmitter disruption.

When hormone levels are evaluated carefully and replaced thoughtfully—with bioidentical estrogen, progesterone, and sometimes low-dose testosterone—the improvement can be profound. That was the case with the reader above.

The Biology Behind Bioidentical Hormones vs. Depression:

The study published in the British Journal of Psychiatry (June 16, 2025) that we referenced above found that hormone therapy, including testosterone, helped ease depression in menopausal women. This aligns with what endocrinologists and menopause specialists have observed for decades: hormones profoundly affect brain chemistry and mood regulation.

Estrogen influences serotonin production and receptor sensitivity. Progesterone affects GABA receptors, which regulate anxiety. Testosterone impacts energy, motivation, and overall sense of well-being. When these hormones plummet during menopause, it’s not surprising that some women experience crushing depression.

Yet conventional psychiatry often treats menopausal depression with antidepressants alone, ignoring the underlying hormonal deficiency. While SSRIs can certainly help some women, others—like our reader—find that addressing the root hormonal imbalance with bioidentical hormones produces far better results.

The Testosterone Factor: The Missing Piece in Hormone Therapy

One of the most frustrating aspects of the hormone therapy debate is how rarely testosterone enters the conversation. Medical education teaches that testosterone is a “male hormone” while estrogen is “female,” but this oversimplification does women a tremendous disservice.

Women absolutely require testosterone. In fact, testosterone is an essential precursor for estrogen production. The enzyme aromatase converts testosterone into estradiol, the most potent form of estrogen. Without testosterone, there can be no estrogen!

How Much Testosterone Do Women Make?

Before menopause, women typically produce testosterone. Normal levels range from 15 to 70 ng/dL, depending on the laboratory. After menopause, many labs consider normal ranges to be 7 to 40 ng/dL. For comparison, men over 60 generally produce 200-850 ng/dL.

While women make far less testosterone than men, this hormone plays critical roles in:

• Energy and vitality
• Libido and sexual satisfaction
• Bone density
• Muscle mass and strength
• Cognitive function and mood
• Motivation and drive

When testosterone levels drop too low, women may experience fatigue, depression, loss of libido, muscle weakness, and diminished sense of well-being—exactly what our reader described during her “10 years of pure hell.”

Why Isn’t Testosterone FDA-Approved for Women?

Here’s the puzzling part: despite decades of off-label use and mounting research evidence, the FDA has never approved testosterone therapy for women. Testosterone is FDA-approved for men, but only under very specific circumstances like testicular failure or pituitary problems.

Many physicians, particularly those specializing in bioidentical hormones and menopause medicine, find this policy frustratingly short-sighted. They’ve seen countless women whose lives were transformed by adding physiologic doses of testosterone to their hormone regimen.

The comprehensive review published in Cureus (Aug. 28, 2024) concluded that testosterone can be especially helpful for easing vaginal dryness and improving sexual desire and satisfaction. But as our reader’s story illustrates, the benefits often extend far beyond sexual function to include mood, energy, and overall quality of life.

Reader Experiences with Bioidentical Hormones and Testosterone:

Over the years, we’ve received numerous testimonials from women whose experiences mirror our reader’s story. Here are just a few:

Cynthia wrote:

“I had a post-menopausal decade of depression, low energy, no libido and creeping osteopenia. Two weeks after starting bioidentical hormone replacement therapy—testosterone and estradiol pellets plus progesterone capsules—the sun came out. My doctor does blood work before every pellet refresh, about every four or five months to adjust the dose if needed. She also takes into account how I’m feeling. My bones are now normal, my sex drive is good, and I haven’t had a problem with testosterone side effects.”

Laurie related:

“At 78, I have been using vaginal testosterone and DHEA cream for years. My new cardiologist is pleased that I am using hormone therapy. Stronger bones, higher libido, heart health and stronger body!”

These stories share common themes: years of suffering, dismissal by conventional doctors, and dramatic improvement with properly balanced bioidentical hormones including testosterone.

Should Many Women Try Testosterone?

Not necessarily. Testosterone therapy is still considered off-label for menopausal symptoms in the U.S., and individualized medical oversight is crucial. But the emerging research, combined with thousands of patient experiences, suggests that testosterone should no longer be ignored in the conversation about menopausal mental health.

The Downsides of Testosterone:

The dose of testosterone is a critical factor. Too much testosterone can cause women some very unpleasant symptoms. Here is what we wrote in this article titled: “Empowering or Risky? Testosterone Therapy in Women and Men:”

“No one should undertake any hormone replacement therapy without careful medical supervision from an experienced health professional. The most common complications of TRT are acne, oily skin, facial hair growth, body hair growth, irritability at high doses and hoarseness. Monitoring blood levels of hormones can help physicians adjust the dose to minimize side effects.

A reader of our syndicated newspaper column described symptoms of excess testosterone:

“At age 29, I had to have a hysterectomy that included my ovaries. After the fat-stored estrogen left my body (producing horrid hot flashes), I complained to my ObGyn about my missing libido. He wrote me a prescription for an estrogen and testosterone mix.

“I began taking them, but I had strange changes in my body. I developed acne, facial hair, body hair and a low voice. I even began to walk differently. It helped some with sex drive, but I felt less and less feminine and more masculine. I hated it. I don’t think testosterone is worth the worry, even for women without ovaries.”

The Women’s Health Initiative: Why Everyone Got Scared

To understand why hormone therapy became so controversial—and why the FDA’s reversal is so significant—we need to revisit the Women’s Health Initiative (WHI) study from 2002.

This massive trial randomized more than 27,000 women to receive estrogen plus progestin (Prempro), estrogen alone (Premarin), or placebo for five to seven years. The results shocked the medical community: women taking estrogen plus progestin showed increased rates of breast cancer and cardiovascular complications.

Almost overnight, hormone therapy went from routine preventive care to something women and doctors feared. Millions of women stopped their hormones abruptly. Doctors became reluctant to prescribe them at all.

But significant critiques of the WHI emerged over time. Most importantly, the average participant age was 63—well past the typical age when women start experiencing menopausal symptoms. Starting hormones more than a decade after menopause may have very different risk-benefit ratios than starting them during the menopausal transition.

Additionally, the WHI used specific synthetic hormones—not bioidentical hormones. As I described above, Premarin contains horse estrogens not found in humans, and Provera (medroxyprogesterone) is a synthetic progestin structurally different from natural progesterone.

Do Bioidentical Hormones Carry Less Risk?

This is the billion-dollar question, and unfortunately, the answer isn’t entirely clear. Large, long-term studies specifically comparing bioidentical hormones to synthetic formulations are limited. There has been no “Women’s Health Initiative” for bioidentical hormones.

Without long-term studies, we have no idea what the long-term consequences are for this kind of therapy. Just because something is natural does not mean that it won’t have a profound impact upon cells, tissues and organs.

However, we do have some informative research. A study published in Acta Endocrinologica (January-March 2021) titled “Progestins and the Risk of Breast Cancer” notes that “…the action of progestogens on the breast is complex and not fully understood.” The authors suggest that synthetic progestin (medroxyprogesterone acetate or MPA) may have a “proliferative” effect on breast tissue. Most oncologists would not perceive that as a benefit.

The authors go on to state that:

“The effect of progestins on breast cancer tumorigenesis may depend on the specific progesterone used for HRT. The interaction between hormone use and progression of breast cancer may be explained by progestin-mediated effects.”

They conclude:

“To sum up, combined hormone therapy was associated with an increased risk for breast cancer. The risk was directly proportional to the duration of use, and in some studies the risk increased from the first 3 years of its use. Depending on progesterone or progestogen, several studies have agreed that natural micronized progesterone and dydrogesterone was associated with a lower to zero risk for breast cancer, compared to other progestogens, while, the risk increased significantly for testosterone-related progestogens, rather than progesterone – related progestogens.”

Confused? I do not blame you. Hormone risk is incredibly confusing. It can take many years to evaluate. Who is going to pay for a Women’s Health Initiative with bioidentical hormones? Do not count on the government or the pharmaceutical industry.

I do come away with the sense that the type of progestin matters—not just whether you’re taking estrogen plus something, but what that something is.

Final Words:

The Bottom Line

For women whose menopause is accompanied by severe depression, anxiety, or profound loss of vitality, bioidentical hormones—including estrogen, progesterone, and a touch of testosterone—may offer relief when nothing else has helped. A very skilled healthcare professional must supervise. Appropriate hormonal testing is essential. And monitoring over time is critical.

As more scientists publish research and FDA shifts its policies, hormone therapy is entering a new era—one in which the experts are finally taking women’s lived experiences seriously.

Please share your own experience with hormone therapy in the comment section below. If you think this article might help someone you know, please share it through email or on social media. Thank you for supporting our work.