My Favorite Meds to De-prescribe

One of the absolute JOYS of my job is weaning patients off chronic medications they were originally put on to manage symptoms of hormone decline.

A sleep aid added in 2019.

A low dose antidepressant added in 2021 "just to take the edge off."

Maybe a blood pressure medication that started around the same time everything else did.

I want to be clear: I never tell a patient to stop a medication on her own, and I'm not suggesting hormone therapy is a replacement for medications you need.

But once hormones are optimized, many women find they no longer need medications that were, in hindsight, treating a hormone-related problem with the wrong tool.

Here are the ones I see most often.

1. Sleep medications

This is the one I revel in the most.

Trazodone, low dose mirtazapine, over-the-counter aids, hypnotics - how I love finally being able to wean someone off!

Insomnia related to hormone decline has real physiology behind it. Estrogen influences serotonin neurotransmission: it increases the expression of tryptophan hydroxylase (the rate-limiting enzyme in serotonin synthesis), inhibits monoamine oxidase (which breaks down serotonin), and modulates serotonin transporter expression, all of which play a role in regulating sleep. Progesterone, through its metabolite allopregnanolone, acts as a positive allosteric modulator of the GABA-A receptor, producing a calming, sedative effect. When both hormones are declining or fluctuating unpredictably, sleep architecture can suffer, night sweats fragment rest further, and a sleep medication gets added to patch the symptom.

When we restore stable estradiol and add oral micronized progesterone at bedtime, many women find they don't need the sleep aid anymore, or need it far less often.

Also in my toolbox: cognitive behavioral therapy for insomnia (CBT-I)! Four MsFLASH trials showed that CBT(i) produced the largest improvement in insomnia symptoms among midlife women with vasomotor symptoms; greater than estradiol, escitalopram, venlafaxine, exercise, or yoga. CBT-I is considered first-line treatment for insomnia in the general population, and current guidelines recommend it for menopausal insomnia as well.

2. Low dose antidepressants and anxiolytics

This one requires nuance, so lend me your patience.

I’m not talking about medication for diagnosed major depressive disorder or an anxiety disorder that predates perimenopause. Those medications are often essential, and hormones are not a substitute for them.

I'm talking about the common scenario where a woman goes to her doctor at 44 or 45 describing new irritability, tearfulness, or anxiety that feels foreign to her, and walks out with an SSRI prescription because it's fast, familiar, and the visit is fifteen minutes long.

While published data may lead one to believe that HRT has little to no effect on anxiety and depression, the clinical experience is consistent: I am repeatedly and regularly weaning women off their SSRIs after HRT is optimized.

3. Gabapentin and clonidine

These are legitimate, evidence-based non-hormonal options, and they're the right call for women who can't or choose not to take hormone therapy. But when a patient comes to me already on one of these purely for vasomotor symptoms, and hormone therapy is a good fit for her, these are quick drops.

The data supports this: systemic estrogen therapy reduces vasomotor symptom frequency by approximately 75%, while nonhormonal options like SSRIs/SNRIs, gabapentin, and clonidine reduce frequency by approximately 40–55%. Estrogen is treating the underlying mechanism; these medications are managing the downstream symptom.

4. Blood pressure medications

I know, I know, this one is probably surprising. Please know, I do not take patients off blood pressure medication casually, and plenty of women need it independent of hormones.

The relationship between menopause and blood pressure is real and complex. Data from the SWAN study showed that some women experience an accelerated rise in systolic blood pressure after menopause, consistent with a hormonal contribution; but this was only one of several trajectory patterns observed, and estradiol levels did not independently predict blood pressure trajectory. Blood pressure tends to increase during menopause coincident with lower estrogen levels, but estrogen decline is rarely the sole factor.

Other factors that increase blood pressure: poor sleep, metabolic dysfunction, increased stress/anxiety. So really - is it any wonder that some women are able to come off their low dose anti-hypertensives?

TL;DR: Why stay on a medication for a symptom that might have a treatable underlying cause? My job isn't to get you off medication for the sake of a shorter list. It's to make sure every medication you're taking is actually the right tool for the job.

Relevant Research:

1. Gu Y, Zhang N, Zhu S, et al. Estradiol Reduced 5-HT Reuptake by Downregulating the Gene Expression of Plasma Membrane Monoamine Transporter (PMAT, Slc29a4) Through Estrogen Receptor β and the MAPK/ERK Signaling Pathway. European Journal of Pharmacology. 2022;924:174939. doi:10.1016/j.ejphar.2022.174939.

2. Li SH, Graham BM. Why Are Women So Vulnerable to Anxiety, Trauma-Related and Stress-Related Disorders? The Potential Role of Sex Hormones. The Lancet Psychiatry. 2017;4(1):73-82. doi:10.1016/S2215-0366(16)30358-3.

3. Hernández-Hernández OT, Martínez-Mota L, Herrera-Pérez JJ, Jiménez-Rubio G. Role of Estradiol in the Expression of Genes Involved in Serotonin Neurotransmission: Implications for Female Depression. Current Neuropharmacology. 2019;17(5):459-471. doi:10.2174/1570159X16666180628165107.

4. Nolan BJ, Liang B, Cheung AS. Efficacy of Micronized Progesterone for Sleep: A Systematic Review and Meta-Analysis of Randomized Controlled Trial Data. The Journal of Clinical Endocrinology and Metabolism. 2021;106(4):942-951. doi:10.1210/clinem/dgaa873.

5. Memi E, Pavli P, Papagianni M, Vrachnis N, Mastorakos G. Diagnostic and Therapeutic Use of Oral Micronized Progesterone in Endocrinology. Reviews in Endocrine & Metabolic Disorders. 2024;25(4):751-772. doi:10.1007/s11154-024-09882-0.

6. Pavicic E, Stute P, Rudzik F, Urech A, Lozza-Fiacco S. No More Sleepless Nights in Perimenopause: An Open-Label, Randomized, Parallel-Group, Active Controlled Intervention Study in Perimenopausal Women With Vasomotor Symptoms and Insomnia to Investigate the Efficacy of Hormone Replacement Therapy and Cognitive Behavioral Therapy for the Treatment of Insomnia: Study Protocol. Trials. 2025. doi:10.1186/s13063-025-09366-9.

7. Guthrie KA, Larson JC, Ensrud KE, et al. Effects of Pharmacologic and Nonpharmacologic Interventions on Insomnia Symptoms and Self-Reported Sleep Quality in Women With Hot Flashes: A Pooled Analysis of Individual Participant Data From Four MsFLASH Trials. Sleep. 2018;41(1). doi:10.1093/sleep/zsx190.

8. Sharma A, Davies R, Kapoor A, et al. The Effect of Hormone Replacement Therapy on Cognition and Mood. Clinical Endocrinology. 2023;98(3):285-295. doi:10.1111/cen.14856.

9. Wu CK, Tseng PT, Wu MK, et al. Antidepressants During and After Menopausal Transition: A Systematic Review and Meta-Analysis. Scientific Reports. 2020;10(1):8026. doi:10.1038/s41598-020-64910-8.

10. Brown L, Hunter MS, Chen R, et al. Promoting Good Mental Health Over the Menopause Transition. Lancet. 2024;403(10430):969-983. doi:10.1016/S0140-6736(23)02801-5.

11. Li Y, Sun Y, Bi Y, et al. Efficacy and Safety of Menopausal Hormone Therapy for Depressive Symptoms in Perimenopausal Women: A Systematic Review and Meta-Analysis. Journal of Affective Disorders. 2026;409:121892. doi:10.1016/j.jad.2026.121892.

12. Gnanasegar R, Wolfman W, Galan LH, Cullimore A, Shea AK. Does Menopause Hormone Therapy Improve Symptoms of Depression? Findings From a Specialized Menopause Clinic. Menopause. 2024;31(4):320-325. doi:10.1097/GME.0000000000002325.

13. Crandall CJ, Mehta JM, Manson JE. Management of Menopausal Symptoms. JAMA. 2023;329(5):405-420. doi:10.1001/jama.2022.24140.

14. Huang AJ, Faubion S, Grady D. Nonhormonal Treatment of Menopausal Vasomotor Symptoms. JAMA Internal Medicine. 2025;185(7):874-875. doi:10.1001/jamainternmed.2025.0990.

15. Samargandy S, Matthews KA, Brooks MM, et al. Trajectories of Blood Pressure in Midlife Women: Does Menopause Matter? Circulation Research. 2022;130(3):312-322. doi:10.1161/CIRCRESAHA.121.319424.

16. Madika AL, MacDonald CJ, Fournier A, et al. Menopausal Hormone Therapy and Risk of Incident Hypertension: Role of the Route of Estrogen Administration and Progestogens in the E3N Cohort. Menopause. 2021;28(11):1204-1208. doi:10.1097/GME.0000000000001839.