Key Takeaways: A retrospective cohort study of 920 perimenopausal and postmenopausal women at the UK's largest specialist menopause clinic, published in The British Journal of Psychiatry (volume 228, issue 5), found that starting or optimizing body-identical hormone therapy cut mean Meno-D mood scores by 44.6% over an average of 107 days. All 12 mood symptoms improved significantly, with energy, concentration, and libido improving the most (59-60% each). Women who also received transdermal testosterone improved numerically more (48.5% vs 45.4%) but the difference was not statistically significant -- likely because the short follow-up and incomplete testosterone dosing underestimated its effect. The study is observational with no placebo arm, so it cannot prove causation, but it is one of the largest real-world datasets documenting that body-identical HRT -- transdermal estradiol, micronized progesterone, and optional testosterone -- meaningfully improves the mood symptoms that cluster around menopause. For women whose low mood, irritability, and anxiety track with the menopause transition, it strengthens the case for treating the hormone change directly rather than reaching for antidepressants first.
What the Study Found
A team led by researchers at a major UK menopause clinic, including Sarah Glynne, Louise Newson, Caroline Gurvich, and Jayashri Kulkarni, published a retrospective cohort study in The British Journal of Psychiatry (228:409-418) titled "Transdermal oestradiol and testosterone therapy for menopausal depression and mood symptoms." It analyzed 920 women treated at the largest specialist menopause clinic in the UK: 448 (48.7%) perimenopausal and 435 (47.3%) postmenopausal. Roughly half were new to hormone therapy and half were having an existing regimen optimized.
Mood was measured with the Meno-D, a validated 12-item questionnaire that scores the severity of 12 menopause-related mood symptoms: low energy, paranoid thinking, irritability, low self-esteem, social isolation, anxiety, somatic symptoms, disrupted sleep, weight concern, low sexual interest, poor memory, and poor concentration. Each item is rated 0 (none) to 4 (severe), so total scores run from 0 to 48.
The headline result: after starting or optimizing body-identical HRT, the mean Meno-D score fell by 44.59% (95% CI -46.83% to -42.34%, P < 0.001) over an average follow-up of 107 days (range 21 to 201 days). Every one of the 12 individual symptoms improved with statistical significance (P < 0.001 for each). The biggest movers were reduced energy, difficulty concentrating, and low libido -- each improving about 59 to 60%. The smallest improvement, paranoid thinking, still dropped 33%.
That is a large, broad effect across the entire mood-symptom cluster, not a narrow benefit on one or two complaints.
The Testosterone Question
The study also compared two treatment strategies. Women on transdermal estradiol with or without a progestogen improved 45.38%. Women who also received transdermal testosterone improved 48.53% -- numerically more, but the difference did not reach statistical significance (P = 0.47).
Two caveats from the authors explain why that comparison should not be read as "testosterone does not help mood." First, the average follow-up was only about three months, and testosterone's effects build over a longer horizon. Second, many of the testosterone users had not yet reached full therapeutic blood levels in that window -- titrating women's testosterone into the right physiologic range takes time. The honest interpretation is that estradiol is the foundation of the mood benefit, and testosterone is a plausible add-on whose contribution this short study likely underestimated. This is consistent with the broader biology of testosterone and mood in women.
Why This Matters: The Misdiagnosis Problem
The clinical importance of this study is not just the numbers. It is what those numbers say about how menopausal mood symptoms are usually handled.
Perimenopause frequently produces new-onset low mood, irritability, anxiety, brain fog, and loss of pleasure -- exactly the cluster the Meno-D measures. When a woman in her mid-40s presents with these symptoms, the default response in primary care has long been an SSRI. But if the underlying driver is the erratic, declining estradiol of the menopause transition, an antidepressant treats the downstream symptom while leaving the cause untouched.
This study shows that when you treat the cause -- restore estradiol with body-identical transdermal HRT, add progesterone for endometrial protection, and consider testosterone -- the entire mood-symptom cluster improves substantially in three months. That is a direct argument for getting the diagnosis right: hormonally-driven perimenopausal mood symptoms are a different clinical entity from primary major depression, and they respond to a different treatment.
This does not mean HRT replaces antidepressants for everyone. Major depressive disorder that is not hormonally driven still needs its own treatment, and some women benefit from both. The point is sequencing and accuracy: for women whose mood symptoms clearly track with the menopause transition, treating the hormone change directly deserves to be on the table first, not as a last resort. Our deeper comparison of HRT versus antidepressants for menopause walks through when each makes sense and when combining them is reasonable.
Where This Fits With Other Recent Evidence
This study does not stand alone. It sits inside a growing body of work pointing the same direction:
Work on HRT and brain fog addresses the cognitive arm of the same symptom cluster.
The convergence matters. No single observational study is decisive, but multiple datasets using different methods keep finding that restoring physiologic hormones improves the mood and cognitive symptoms of the menopause transition.
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The study used a specific kind of hormone therapy, and the distinction matters for anyone trying to act on the findings.
Transdermal 17-beta-estradiol. Estradiol delivered through the skin by patch or gel, rather than swallowed as a pill. Transdermal delivery avoids the first-pass liver metabolism that drives the clotting risk historically associated with older oral estrogens, which is why modern menopause practice favors it.
Micronized progesterone (or, for some women, a levonorgestrel intrauterine system). Used to protect the uterine lining in women who still have a uterus. Micronized progesterone is structurally identical to the body's own progesterone and has a more favorable mood and breast-tissue profile than the older synthetic progestins used in the early Women's Health Initiative era.
Transdermal testosterone in the women who received it -- a low-dose cream or gel titrated toward the upper end of the premenopausal physiologic range, not a male dose.
Together this is what clinicians mean by "body-identical" or "bioidentical" HRT: hormones with the same molecular structure as the ones the ovaries make, delivered in ways that match physiology. If you want the full breakdown of why structure and delivery route matter, see bioidentical versus synthetic HRT for women.
The reason this matters for the mood finding: the study's results apply to this kind of HRT. A clinic prescribing oral synthetic estrogen-progestin combinations is not delivering the same regimen the study evaluated.
How Fast, and What to Expect
The average follow-up here was about 107 days -- a little over three months -- and that window was enough to produce a 45% drop in mood scores. In practice, women on properly dosed body-identical HRT often notice early shifts in sleep, irritability, and energy within the first few weeks, with mood and cognitive benefits continuing to build over months.
The authors flagged the short follow-up as a likely underestimate of the full benefit, which is an important framing for patients. If you start a regimen and your mood is partially -- but not fully -- better at six weeks, that is not a treatment failure. It is the expected mid-trajectory of a process that keeps improving as estradiol stabilizes and, where used, testosterone reaches therapeutic levels.
A reasonable evaluation window is 3 to 6 months on a titrated regimen, with a check-in and lab review partway through, before concluding whether the approach is working.
The Limitations You Should Know
This is a strong real-world dataset, but it has clear limits, and reading it honestly means stating them.
No control group. It is observational with no placebo or untreated comparison arm. Some of the improvement could reflect placebo response, regression to the mean, or natural fluctuation of perimenopausal symptoms. This study cannot prove causation; only a randomized controlled trial can.
Narrow population. About 94.5% of participants were White British women accessing private healthcare. The findings may not generalize cleanly to other populations or to publicly-funded care settings.
Short and variable follow-up. The 21-to-201-day range means some women were assessed early, which the authors note may underestimate benefit -- but it also limits conclusions about durability.
Unmeasured confounders. Changes in antidepressant use, medication adherence, and other menopausal symptoms affecting mood were not fully tracked.
The authors are explicit that prospective randomized trials with longer follow-up are needed. None of these caveats erase the finding -- a 45% improvement across a large cohort with very low p-values is not noise -- but they place it correctly: strong supportive evidence, not definitive proof.
What This Means for Choosing Care
The findings translate cleanly into what to look for in a menopause or HRT clinic. A clinic practicing in line with this evidence will:
Prescribe transdermal estradiol (patch or gel), not oral synthetic estrogen, as the foundation for mood symptoms.
Use micronized progesterone or an appropriate intrauterine option for endometrial protection, rather than older synthetic progestins.
Consider adding testosterone when energy, mood, concentration, and libido symptoms persist on estradiol alone, with proper titration and lab monitoring -- see our women's testosterone dosage guide for what that looks like.
Re-check labs during titration, not set a single fixed dose and walk away.
Take a real differential -- ruling out thyroid disease, iron deficiency, sleep apnea, and primary major depression -- rather than treating every symptom as hormonal or, conversely, reaching reflexively for an SSRI.
A clinic that does the opposite -- oral synthetics, no testosterone option, no titration, or an automatic antidepressant for clearly hormonal mood symptoms -- is not practicing to the current evidence. Our best online HRT clinic for women comparison and the broader clinic comparison identify clinics that follow these standards, with transparent scoring on diagnostics, monitoring, and protocol quality.
The Bottom Line
The most useful framing of this study is not "HRT cures depression." It is that the mood symptoms women experience during the menopause transition -- low mood, irritability, anxiety, anhedonia, brain fog, fatigue -- respond substantially and broadly to body-identical hormone therapy, with a 45% mean improvement in three months across nearly 1,000 women. Testosterone likely adds further benefit that this short study underestimated.
For women being handed an antidepressant for symptoms that started with their cycles changing, that is a reason to ask a different question: is this hormonal, and has anyone tried treating the hormone change directly? The evidence increasingly says that question deserves an answer before the prescription pad comes out.
Glynne S, Kamal A, McColl L, Newson L, Reisel D, Mu E, Hendriks O, Saini P, Gurvich C, Kulkarni J. Transdermal oestradiol and testosterone therapy for menopausal depression and mood symptoms: retrospective cohort study. The British Journal of Psychiatry. 2025;228(5):409-418. Cambridge Core | PubMed 40519046
Kulkarni J, Gavrilidis E, Hudaib AR, et al. Development and validation of a new rating scale for perimenopausal depression-the Meno-D. Translational Psychiatry. 2018;8:123. Nature
Davis SR, Baber R, Panay N, et al. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab. 2019;104(10):4660-4666. PMC Article
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Frequently Asked Questions
What did the British Journal of Psychiatry HRT depression study find?
A retrospective cohort of 920 perimenopausal and postmenopausal women at the UK's largest specialist menopause clinic found that starting or optimizing body-identical hormone therapy reduced mean Meno-D mood scores by 44.6% (95% CI -46.8% to -42.3%, P < 0.001) over an average of 107 days. All 12 individual mood symptoms improved significantly (P < 0.001 each), with energy, concentration, and libido improving the most at 59-60% each. The study was published in The British Journal of Psychiatry, volume 228, issue 5, pages 409-418.
Did adding testosterone improve menopausal mood more than estradiol alone?
Numerically yes, but the difference was not statistically significant. Women on transdermal estradiol plus or minus a progestogen improved 45.4%, while women who also received transdermal testosterone improved 48.5% (P = 0.47). The authors noted the short 3-month follow-up and the fact that many testosterone users had not yet reached full therapeutic blood levels likely underestimated testosterone's contribution. The takeaway is that the foundation is estradiol, and testosterone is an add-on that may help further, not a standalone antidepressant.
Is HRT a treatment for clinical depression in menopause?
This study supports HRT for the low-mood, irritability, anxiety, and anhedonia that cluster around the menopause transition -- often called perimenopausal or menopausal mood symptoms. It is not evidence that HRT replaces antidepressants for major depressive disorder unrelated to hormones. The clinical reality is that hormonally-driven mood symptoms in perimenopause are frequently misdiagnosed as primary depression and prescribed SSRIs first. For women whose mood symptoms track with the menopause transition, the evidence increasingly supports treating the hormone change directly.
How fast does HRT improve menopausal mood symptoms?
In this study the average follow-up was about 107 days (roughly 3 months), and women showed a 45% mean reduction in mood scores in that window. Some mood and energy benefits appear within the first weeks, but the authors specifically noted that the relatively short follow-up may have underestimated the full benefit, because both estradiol optimization and testosterone build over months. A reasonable evaluation window is 3 to 6 months on a properly titrated regimen before judging response.
What does body-identical HRT mean and why does it matter here?
Body-identical (or bioidentical) HRT uses hormones structurally identical to those the body makes: transdermal 17-beta-estradiol delivered by patch or gel, micronized progesterone, and transdermal testosterone. The study used exactly this combination. Transdermal estradiol avoids the first-pass liver effect and the clot risk associated with older oral estrogens, and micronized progesterone has a more favorable mood and breast profile than older synthetic progestins. See our guide on bioidentical versus synthetic HRT for the full comparison.
How should this change how I choose a menopause or HRT clinic?
Look for a clinic that prescribes transdermal (not oral) estradiol, uses micronized progesterone rather than older synthetic progestins, will add testosterone when mood, energy, and libido symptoms persist, and re-checks labs during titration rather than using one fixed dose. A clinic that reflexively reaches for antidepressants for clearly hormonal mood symptoms -- or refuses to consider testosterone -- is not practicing to this evidence. See our women's HRT clinic comparison for clinics that follow these standards.
