9 Supplements for Perimenopause Mood Swings

Mood swings in perimenopause are not inevitable — and they’re not untreatable. While hormone therapy is the most effective approach for many women, there are a number of supplements with evidence or strong clinical rationale for supporting mood stability during the hormonal turbulence of perimenopause. Here are nine worth knowing about, along with the context you need to use them wisely.

1. Magnesium Glycinate

Magnesium is one of the most consistently beneficial supplements for perimenopausal mood symptoms. It supports GABA activity (your brain’s calming system), reduces HPA axis reactivity (the stress response), improves sleep quality, and helps regulate the inflammatory processes that worsen during perimenopause. Many women are magnesium-deficient due to dietary insufficiency, stress depletion, and alcohol consumption — and this deficiency is amplified during hormonal transition. Magnesium glycinate (200–400 mg at bedtime) is gentle, well-absorbed, and has a natural calming effect that supports both mood and sleep. I recommend it as the first supplement for almost every perimenopausal woman I see experiencing mood instability, irritability, or sleep disruption. It’s safe, inexpensive, and evidence-informed.

2. Ashwagandha

Ashwagandha (Withania somnifera) is an adaptogenic herb with powerful evidence for reducing cortisol, improving stress resilience, and supporting hormonal balance. For perimenopausal women, whose HPA axis (stress response system) is frequently dysregulated due to hormonal fluctuations, ashwagandha provides meaningful support. Several studies have shown ashwagandha to reduce self-reported stress, anxiety, and menopausal symptom scores. It also has a mild testosterone-supporting effect in women and can be gently supportive of thyroid function. Standardized extracts (KSM-66, 300–600 mg daily) are the most studied and reliable forms. Use with caution if you have autoimmune thyroid disease, and avoid during pregnancy. It’s one of the most versatile and well-evidenced adaptogens available for perimenopausal stress and mood support.

3. Vitamin B6

B6 is a cofactor for serotonin, dopamine, and GABA synthesis — the very neurotransmitters most implicated in perimenopausal mood disruption. Several studies have found that B6 supplementation reduces premenstrual mood symptoms (depression, irritability, anxiety) — and similar mechanisms apply to the mood swings of perimenopause, which are in part driven by the same estrogen-serotonin relationship. B6 also supports progesterone sensitivity in the brain (helping the brain respond to what progesterone remains). The active form, pyridoxal-5-phosphate (P5P), is better utilized by those with MTHFR variants. A typical dose is 25–50 mg daily of P5P. B6 in high doses (above 200 mg daily for extended periods) can cause peripheral neuropathy, so stay within recommended ranges and test before supplementing if possible.

4. Evening Primrose Oil

Evening primrose oil (EPO) is a plant-based source of gamma-linolenic acid (GLA), an omega-6 fatty acid with anti-inflammatory effects that differs from most dietary omega-6s. EPO has been used traditionally for PMS and menopausal symptoms, and several small trials suggest it reduces hot flash frequency, breast tenderness, and mood-related symptoms. Its mechanism is thought to involve prostaglandin modulation and support for cell membrane fluidity. EPO is generally safe and well-tolerated in doses of 500–3,000 mg daily. It is not recommended for women on blood thinners, and large amounts may lower seizure threshold in those with epilepsy. While the evidence for EPO is less robust than for some other supplements on this list, it has a long history of use, a reasonable safety profile, and many women find it helpful for breast tenderness and mood symptoms specifically.

5. Black Cohosh

Black cohosh (Actaea racemosa) is one of the most studied herbs for menopausal and perimenopausal symptoms. Multiple clinical trials and meta-analyses have found it effective for reducing hot flashes, night sweats, and — relevant here — mood symptoms including anxiety, irritability, and depression associated with menopause. It is not a phytoestrogen (it doesn’t act on estrogen receptors directly), which makes it an option even for women who have had hormone-sensitive cancers, though this should always be discussed with your oncologist. The most studied product is Remifemin (a standardized black cohosh extract), used at 20 mg twice daily. Black cohosh should not be used during pregnancy and is generally recommended for a maximum of 6 months of continuous use, though some clinicians extend this with monitoring. Liver toxicity has been rarely reported; use reputable brands with quality testing.

6. Saffron

Saffron has a growing evidence base for mood support in the peri-menopausal context. Beyond its antidepressant properties (discussed in the depression article), saffron has been shown in clinical trials to reduce menopausal hot flashes and mood symptoms. A 2021 randomized trial in Nutrients found that 30 mg/day of saffron extract significantly improved hot flash severity and psychological symptoms including anxiety and depression in menopausal women. Its mechanisms include serotonin reuptake inhibition, antioxidant activity, and anti-inflammatory effects. Saffron extract (standardized to crocin/safranal content, 30 mg daily) is well-tolerated and has an excellent safety profile. It’s a particularly good option for women whose perimenopausal symptoms include both hot flashes and mood disruption — addressing both simultaneously.

7. Omega-3 Fatty Acids

Omega-3s support perimenopausal mood through multiple mechanisms: reducing neuroinflammation, supporting serotonin and dopamine signaling, improving sleep quality, and reducing the cardiovascular and metabolic changes that accompany hormonal transition. EPA in particular appears most relevant for mood support. Research in menopausal women has found that omega-3 supplementation can reduce depression and anxiety scores and may also reduce hot flash frequency in some women. A therapeutic dose is 2–4 grams EPA+DHA daily, with EPA predominant. Omega-3s are also broadly important for cardiovascular health — a major concern during perimenopause as estrogen’s cardioprotective effects wane. This makes omega-3s one of the most multifunctional supplements for perimenopausal health and a strong component of any comprehensive perimenopause support protocol.

8. DHEA (With Medical Guidance)

DHEA (dehydroepiandrosterone) is an adrenal hormone that serves as a precursor to both estrogen and testosterone. Levels decline significantly with age, and low DHEA is associated with fatigue, low libido, depressed mood, and cognitive decline. Supplementation with DHEA at low doses (typically 5–25 mg daily) has been studied for menopausal symptoms, libido, and mood with generally positive results. However, DHEA is a hormone — not a simple supplement — and it can convert to either estrogen or testosterone in the body, with variable and individual-specific effects. It should not be used without medical supervision and ideally should be guided by DHEA-S (DHEA-sulfate) blood testing. Low-dose vaginal DHEA (Intrarosa) is FDA-approved for vaginal atrophy. Oral or topical DHEA for systemic effects requires individualized clinical guidance and regular monitoring.

9. Bioidentical Progesterone (With MD)

Bioidentical progesterone — derived from plant sources and chemically identical to the progesterone produced by the ovaries — is one of the most effective and underutilized tools for perimenopausal mood symptoms, sleep disruption, and anxiety. Unlike synthetic progestins (like medroxyprogesterone acetate), bioidentical progesterone maintains GABA-A receptor activity, providing a calming, anxiolytic, sleep-promoting effect. Many perimenopausal women are progesterone-deficient (due to anovulatory cycles) years before their estrogen significantly declines, and low progesterone is a primary driver of mood instability, sleep disruption, and anxiety in early perimenopause. Low-dose bioidentical progesterone (100 mg oral micronized progesterone at bedtime — Prometrium, or compounded) is available by prescription and, when appropriately prescribed, is remarkably effective. Always work with a knowledgeable clinician for hormonal prescriptions.

Perimenopause is a significant hormonal transition that your mental health deserves full support through. At drlewis.com, I offer comprehensive perimenopause evaluations that integrate hormonal assessment, psychiatric expertise, and functional medicine — because your brain and your hormones are part of the same system. Brooklyn and telehealth available.