Ninety percent.

That's my honest accounting of what testosterone did for the flatness I wrote about last time. The motivational deadness that my antidepressant couldn't touch, the one that took my 40s and convinced me it was wisdom, lifted almost all the way when I restored my testosterone.

Almost.

There's a residue. It's small, and I notice it, and I've spent the past several months reading everything I could find about what to do with it.

This article is what I found. Some of it's useful. A lot of it's thinner than the people selling it want you to believe. And one piece of it genuinely surprised me.

What ten percent feels like.

It isn't dramatic. That's the thing that makes it hard to describe and easy to dismiss.

The pull is back. I start things again. I finished the research for this article, which is not a small tell, because two years ago I'd have organized it into a folder and felt fine about that.

But there are afternoons where the warmth is a half step down. Days where the work is good and I do it anyway, and it takes a push that I don't think it should take.

I know the difference between this and the flatness I had before, the way you know the difference between a room that's dim and a room that's dark. It's not the same problem. It's a remainder of it.

So I did what I do. I went to the literature.

Estrogen is the other dopamine lever.

Here's the part I didn't expect, and it reframed how I think about my own regimen.

In the last article I explained that testosterone acts on the dopamine system: it raises tyrosine hydroxylase, the enzyme that builds dopamine, and it works on androgen receptors in the ventral tegmental area, where the brain's wanting signal starts.

What I didn't know is that estrogen does a version of the same job.

Five separate papers in my library, working independently, describe the same mechanism. Estrogen upregulates tyrosine hydroxylase, the same enzyme. It modulates the dopamine transporter and dopamine receptor sensitivity. It acts through estrogen receptor alpha in the basal ganglia, one of the brain's core motor and motivational regions.

When estrogen drops, dopamine transmission is impaired. The reviews name the consequence directly: reduced motivation, cognitive inflexibility, anhedonia. In ovariectomized rats, estrogen loss measurably lowers dopamine in the lateral habenula. (Refs: Transl Neurosci 2026, doi:10.1515/tnsci-2025-0399; Brain Sci 2025, doi:10.3390/brainsci15091003; Int J Mol Med 2025, doi:10.3892/ijmm.2025.5656)

Two hormones. One reward circuit. Both of them decline in the menopause transition, and medicine talks about one of them in terms of hot flashes and the other one barely at all.

I want to be careful here, because this is exactly the point where a wellness article would tell you estrogen fixes anhedonia. It doesn't say that.

The mechanism is well described. The clinical evidence is a different story, and I'll get to how thin it is.

But if you're on estrogen for hot flashes and sleep, you may be getting something else you were never told about. And if you're not on it, this is a question worth asking, for reasons that have nothing to do with temperature.

Exercise has the best human evidence, and it comes with an asterisk.

This is the one intervention with real data in women who actually look like us.

A 2025 systematic review and network meta-analysis pooled 23 randomized controlled trials covering 2,155 peri- and post-menopausal women, comparing types of physical activity head to head. (BMC Public Health 2025, doi:10.1186/s12889-025-24398-1)

The ranking, by probability of being the most effective:

• Aerobic exercise: 78.7% (walking, cycling, running; 12 trials)
• Multi-mode exercise: 78.1% (aerobic plus strength plus flexibility; 4 trials)
• Stretching: 72.6% (4 trials)
• Mind-body: 45.4% (yoga, Pilates, qigong; 8 trials)

Aerobic and multi-mode are essentially tied at the top. Mind-body finished last, which will annoy some people, and the authors are fair about why: yoga may need longer than these trials ran to show its effect.

Now the asterisk, and it's a real one.

Every one of those trials measured composite depression scales. Not one measured anhedonia. HAM-D, BDI, PHQ-8, and similar. Those instruments contain an item or two that brush against loss of interest, but they're built to capture depression as a whole, and they report it as one number.

So this is evidence that exercise helps depressive symptoms in menopausal women. It's an inference, not a finding, that it helps the specific motivational flatness we're talking about.

There's a second problem. Egger's test for publication bias came back significant at p = 0.002. In plain terms, the small trials that found nothing appear to be missing from the literature, which means the real effect is probably smaller than the pooled number suggests.

I'm telling you this because I'd rather hand you a smaller true thing than a bigger convenient one.

Exercise is still what I'd put first among everything that isn't a hormone. The data are the best available, the mechanism is plausible, and the downside is a pair of shoes.

A note on which exercise, because the mechanism data disagree with the ranking data.

There's an interesting wrinkle worth knowing if you're choosing between the treadmill and the squat rack.

A 2026 review traced how exercise touches the endocannabinoid system, which feeds directly into the reward circuit through CB1 receptors in the nucleus accumbens and the VTA, the same real estate the hormones are working on. (Front Psychiatry 2026, doi:10.3389/fpsyt.2026.1766980)

Moderate aerobic exercise raises circulating anandamide and 2-AG, the body's own cannabinoids. That's the runner's-high chemistry, and it lands on the reward system.

Resistance training does the opposite to those particular molecules. Four weeks of it lowered them.

Before anyone reads that as "don't lift," understand what it means and doesn't.

It's one narrow biomarker pathway, in a narrative review, with no anhedonia measures anywhere in it. Strength training earns its place in your week on bone density, muscle, and metabolic health, and none of that is in question.

The review's own read is that resistance training likely helps mental health through neuroplasticity instead, by a different door.

But if the target is specifically the flatness, the mechanistic case points at moderate aerobic work. That happens to agree with the clinical ranking, which is the kind of agreement worth noticing.

Walking counts. It's in twelve of those trials.

The honest hierarchy.

Here's my ranking of everything I looked at, sorted by how much weight the evidence actually bears. I'm a medical technologist, not a physician, and this is my read of the literature, not a treatment plan. Take it to someone who can see your chart.

Worth doing, best available evidence:

• Moderate aerobic exercise. 23 RCTs, 2,155 menopausal women, top of the ranking. Measured depression, not anhedonia. Publication bias present. Still the strongest thing on this list.
• Estrogen, if it's appropriate for you. One RCT cited in a 2025 review reported 68% remission of depressive symptoms versus 17% on placebo. (doi:10.3892/ijmm.2025.5656) That's a striking number and I want to flag every limit on it: it reaches me through a narrative review rather than the primary paper, it measured general depressive symptoms, and it's one trial. The mechanism section above is the stronger argument here, not this number.

Plausible, unproven, low risk:

• Sleep and circadian regularity. The mechanistic literature keeps circling back to it. No trial measured it against anhedonia in this population.
• Mediterranean-pattern eating. Reviewed as supporting microbial diversity and lower inflammation. No anhedonia data at all.

Oversold, and I'll name it:

• Probiotics. You'll see a real number attached to these: a pooled effect of SMD −0.997 for anxiety in women during hormonally dynamic phases. (Cited in Nutrients 2026, doi:10.3390/nu18050743) That's a legitimate finding. It's also about anxiety, and the review states plainly that it offers nothing on anhedonia, motivation, or the dopamine wanting signal. Anxiety and anhedonia are different problems. Watch how often that number gets recycled as if they're the same.
• Vitamin D. This is the one that taught me the most about how claims get built. In the entire body of work I read, exactly one intervention was ever measured against anhedonia directly. It was vitamin D. It increased sucrose preference and raised dopamine transporter density in the nucleus accumbens. In rats. A single rat study, under chronic mild stress, cited inside a narrative review. (doi:10.3390/ijms27073243) No humans. No women. No menopause. If you've seen vitamin D sold for motivation, that's a rodent standing on a very long chain of citations. Test your level and correct a deficiency because deficiency is worth correcting. Don't expect your drive back from it.
• Mitochondrial antioxidants (CoQ10, NAC, alpha lipoic acid, curcumin, resveratrol, MitoQ). Every result is preclinical. The reviews are candid: no human trials in perimenopausal mood disorders. The supplement aisle is not candid.

Why you can't get a straight answer about this.

I want to name the thing underneath all of these caveats, because it's the actual story.

Fifteen full-text papers. Six had anything usable about interventions at all. Across every one of them, exactly one intervention had ever been measured against anhedonia as an outcome, and it was tested in rodents.

Not one human trial in this entire literature made anhedonia an endpoint in menopausal women.

That's the same hole I found writing about testosterone, where the strongest signal we have (56% response for loss of interest, the highest of any symptom measured in 510 women) comes from an uncontrolled observational study, because the randomized trial has never been run.

The pattern holds no matter which lever you look at. Everyone measures depression. Depression scales average the flatness into a composite with sadness, sleep, appetite, and guilt, and out comes a single number that can't tell you which of those moved.

So a woman whose depression is managed and who still can't start anything gets told her scores look fine.

Her scores do look fine. The instrument was never built to see what's wrong with her.

This isn't a conspiracy, it's incentives. There's no FDA-approved testosterone product for women, so there's no sponsor for that trial. Estrogen is generic. Exercise has no patent holder. Anhedonia in midlife women is a question with no commercial owner, so it stays unasked.

What I actually do.

Since I'm asking you to discount most of what's out there, here's my own accounting, offered as one person's approach and not as advice.

I'm on testosterone, and it did the heavy lifting. Ninety percent. I've written about the labs and the test codes in the previous article, and that's still where I'd tell anyone to start.

I'm on estrogen gel, two pumps every morning, plus oral micronized progesterone at night. I started that regimen for the symptoms everyone talks about.

Reading this literature changed what I think it's doing. I now suspect the estrogen has been quietly holding up part of the dopamine system this whole time, which is not something anyone mentioned when I started it.

I can't prove that about myself. Nobody can, because the study doesn't exist. But it reframed a drug I thought I understood.

I walk. Not as a protocol, just most days. It's the intervention with the best evidence in women my age and I'd be a hypocrite to rank it first and skip it.

I lift, for my bones and my muscle, and I've stopped expecting it to do anything for the flatness specifically.

I don't take the antioxidant stack. The evidence is rats.

And I've made a kind of peace with the ten percent. Not a resigned peace. I keep reading. But I'm 57, I've been on an antidepressant for 30 years, I have two copies of APOE4, and I've learned that "most of it, most of the time" is a real outcome and not a failure.

There's a version of this article that promises the last ten percent is solvable if you buy the right thing. I don't have that article. What I have is a mechanism that's well described, one intervention with decent data, and a research gap where the answer should be.

If this is you.

If you read the testosterone piece and got your labs and it helped, and there's still a remainder, you're not doing it wrong. You've found the edge of what's known.

If you're on estrogen already, you might be getting more than you were told. That's worth knowing.

If you're not, and the flatness is the symptom you care about, the estrogen-dopamine mechanism is a legitimate thing to raise with a menopause specialist. Not as a cure. As a question the research supports asking.

And if you're waiting for the trial that measures this properly, so am I. It hasn't been funded, because the women it would help aren't a market.

Go for the walk anyway. It's the best-supported thing on the list, and it's free.

If you know someone who got the flatness half-fixed and thinks that's where the story ends, send them this.

I write SmartStrongAlive because "it's just aging" was never a good enough answer. If that sounds like a question you've been asking too, you can subscribe below.

Sources

1. Wang et al. Effects of different physical activity interventions on depressive symptoms in menopausal women: a systematic review and network meta-analysis. BMC Public Health. 2025. doi:10.1186/s12889-025-24398-1. 23 RCTs, n=2,155 peri/postmenopausal women. Aerobic SUCRA 78.7%, multi-mode 78.1%, stretching 72.6%, mind-body 45.4%. Outcomes were composite depression scales, not anhedonia. Egger's test p=0.002 indicating publication bias.
2. Wang et al. Research advances on estrogen deficiency leading to depression. Translational Neuroscience. 2026. doi:10.1515/tnsci-2025-0399. Narrative review. Estrogen upregulates tyrosine hydroxylase and dopamine beta-hydroxylase, modulates DAT and receptor sensitivity; estrogen loss reduces lateral habenula dopamine in ovariectomized rats.
3. Cho et al. Beyond Hot Flashes: The Role of Estrogen Receptors in Menopausal Mental Health and Cognition. Brain Sciences. 2025;15(9):1003. doi:10.3390/brainsci15091003. Narrative review. Estrogen acts via ERα in basal ganglia to modulate dopamine signaling underlying motivation and reward; estrogen loss linked to anhedonia and reduced motivation.
4. Yu et al. Mitochondrial dysfunction in perimenopausal mood disorders: from hormonal shifts to neuroenergetics. International Journal of Molecular Medicine. 2025. doi:10.3892/ijmm.2025.5656. Narrative review. Cites an RCT reporting 68% remission with 17-beta-estradiol vs 17% placebo (general depressive symptoms, not anhedonia). Mitochondria-targeted antioxidants are preclinical only.
5. Zhang et al. Bridging reward and resilience: the endocannabinoid system as a unifying mechanism in exercise. Frontiers in Psychiatry. 2026. doi:10.3389/fpsyt.2026.1766980. Narrative review. Moderate aerobic exercise raises AEA and 2-AG acting on CB1 receptors in nucleus accumbens and VTA; resistance training lowered these markers. No anhedonia outcomes.
6. Vesković et al. Vitamin D as a Regulator of the Biological Clock. International Journal of Molecular Sciences. 2026. doi:10.3390/ijms27073243. Narrative review. Cites a single rat chronic-mild-stress study in which vitamin D increased sucrose preference and nucleus accumbens dopamine transporter density. No human anhedonia data.
7. Marano et al. The Gut Microbiota in Perimenopausal Anxiety. Nutrients. 2026. doi:10.3390/nu18050743. Narrative review. Cited probiotic meta-analysis SMD −0.997 (95% CI −1.684 to −0.311, p=0.004) for anxiety in hormonally dynamic phases. Review explicitly reports no evidence on anhedonia or motivation.
8. Glynne S, Kamal A, Kamel AM, Reisel D, Newson L. Effect of transdermal testosterone therapy on mood and cognitive symptoms in peri- and postmenopausal women: a pilot study. Archives of Women's Mental Health. 2024;28(3):541-550. doi:10.1007/s00737-024-01513-6. Observational, n=510; loss of interest had the highest response rate at 56%.