Beyond the Brain: How Hormones Are Rewriting the Story of Depression and Anxiety

For decades, the dominant narrative in mental health has centered on the brain. From neurotransmitters like serotonin and dopamine to therapies aimed at rewiring cognitive patterns, depression and anxiety have long been treated as purely cerebral conditions. But now, a growing body of research is challenging that view—and offering new hope to the millions who don’t find relief from conventional treatments.

According to the World Health Organization, more than 280 million people globally suffer from depression, with anxiety disorders affecting another 301 million. Antidepressants and cognitive behavioral therapy (CBT) remain first-line treatments, but for about one-third of patients with major depressive disorder, these strategies don’t work. This has prompted researchers to look beyond the brain—and toward an often-overlooked player: the endocrine system.

Hormones such as estrogen, progesterone, testosterone, cortisol, and thyroid hormones play a critical role in regulating bodily systems. But their influence extends far beyond metabolism or reproduction. “Hormones are deeply intertwined with emotional regulation, memory, motivation, and stress resilience,” says Dr. Jennifer Payne, Director of the Reproductive Psychiatry Research Program at Johns Hopkins University.

New studies now suggest that for some individuals, hormonal imbalances may not be just a side effect of mood disorders—but a root cause.

A recent meta-analysis published in The Lancet Psychiatry found that individuals with hypothyroidism were twice as likely to develop depression. Another study led by Oxford University showed that hormone replacement therapy (HRT) significantly reduced the need for antidepressants among menopausal women, suggesting that correcting hormonal deficits may have mood-stabilizing effects.

In cases of treatment-resistant depression (TRD), where patients fail to respond to two or more standard therapies, hormonal imbalances are emerging as a common denominator. Dr. Hadine Joffe, Executive Director of the Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, notes, “Perimenopause and postpartum periods are windows of extreme hormonal fluctuation—and also periods of increased psychiatric vulnerability. Ignoring this is a disservice to our patients.”

Indeed, a 2023 study involving over 130,000 women published in JAMA Psychiatry found a sharp spike in mood disorders like depression and bipolar disorder during perimenopause and the year following childbirth. Notably, many affected women didn’t exhibit classic symptoms like persistent sadness, but rather vague signs like fatigue, anxiety, and mental fog—often dismissed or misdiagnosed.

While hormonal health in women has started to gain attention, the conversation around men is lagging. Testosterone deficiency, or hypogonadism, is increasingly recognized for its psychological toll. Symptoms include irritability, low mood, fatigue, and even cognitive decline.

“Testosterone replacement therapy (TRT) is still stigmatized due to its association with anti-aging and fitness marketing,” says Dr. Bradley Anawalt, Chief of Medicine at the University of Washington Medical Center. “But in clinically diagnosed cases, it can be life-changing for mood and mental clarity.”

A 2022 review in Psychoneuroendocrinology confirmed that men with low testosterone who received TRT experienced statistically significant improvements in depressive symptoms compared to placebo.

Despite mounting evidence, hormonal evaluations remain rare in psychiatric assessments. In men, a simple blood test can often confirm hormone levels. But in women, the task is more complex due to monthly hormonal fluctuations. Clinicians frequently fail to ask about menstrual irregularities, postpartum changes, or contraceptive use—factors that could flag an underlying endocrine issue.

“We’re still practicing brain-centric psychiatry,” says Dr. Laura Payne, Clinical Psychologist at Harvard Medical School. “But emotional health is biochemical, and hormones are chemical messengers. To leave them out of the equation is to ignore a key piece of the puzzle.”

The future of mental health care may lie in a more integrative approach—one that blends psychological insight with physiological data. Clinical trials are now underway to test hormone-based interventions in targeted subgroups of patients with depression and anxiety. The goal: personalized treatment based not only on symptoms, but also on biology.

In the meantime, experts urge both clinicians and patients to advocate for comprehensive screenings. “If you’re experiencing depression or anxiety that doesn’t respond to typical treatment,” says Dr. Joffe, “ask about hormone testing. Especially if you’re going through a life phase like menopause, postpartum, or midlife changes.”

We’re just beginning to understand how intricately the brain and the body communicate. But the implications are clear: treating mental health as a purely neurological issue may be limiting our ability to heal.

As Dr. Anawalt puts it, “The brain doesn’t operate in a vacuum. It listens to the rest of the body. And it’s time our treatment models did the same.”