In This article

• Attitudes regarding menopausal hormone therapy have shifted with newer data and recent FDA label changes.
• Menopausal hormone therapy is considered to be a reasonable treatment option for women under the age of 60 who are within 10 years of their last menstrual period.
• While there are data to indicate that estradiol can improve mood and reduce anxiety symptoms, menopausal hormone therapy is not considered to be a first-line treatment for depression or anxiety in perimenopausal women. 
•  Hormone therapy may be considered in women who partially respond to traditional antidepressants and in women who experience PMDD or worsening premenstrual symptoms during the menopausal transition.
• Collaboration with gynecologists and primary care providers can help to integrate HRT into the comprehensive care of women with perimenopausal symptoms, including depression and anxiety.

We have seen a marked increase in the number of perimenopausal and early postmenopausal women presenting with questions about hormone therapy. These patients typically present with a constellation of symptoms, including depression, irritability, sleep disturbance, cognitive difficulties, and fatigue. This shift likely reflects growing awareness of the burden associated with the menopausal transition and a major change in how hormone replacement therapy (HRT), now more often termed menopausal hormone therapy (MHT), is viewed in the medical community. 

In 2025, the FDA initiated the removal of the broad black box warnings about cardiovascular disease, breast cancer, and probable dementia associated with systemic menopausal hormone therapies, concluding that earlier labels overstated risk when applied to appropriately selected, younger symptomatic women. A boxed warning for endometrial cancer remains in place for estrogen-alone products used in women with an intact uterus.

For mental health providers, these changes raise important questions: When should we consider HRT in women with mood and anxiety symptoms emerging in the menopausal transition? How should we counsel patients about benefits and risks? And how do current guidelines inform collaborative care with gynecology and primary care colleagues?

Changing Attitudes Toward Hormone Therapy

Before publication of the Women’s Health Initiative (WHI) findings in the early 2000s, HRT was routinely prescribed to perimenopausal and early postmenopausal women to manage vasomotor symptoms, sleep disturbance, mood and cognitive changes, fatigue, and sexual dysfunction. It was also commonly continued long term with the goal of reducing risk of osteoporosis and cardiovascular disease. These prescribing patterns were based largely on observational data and pathophysiologic reasoning rather than randomized trials in midlife women.

The initial WHI reports raised concerns about increased risk of venous thromboembolism, stroke, and breast cancer with specific oral estrogen–progestin regimens in women who were, on average, older and many years beyond the final menstrual period. Subsequent reanalyses clarified that absolute risks differed substantially by age and time since menopause, with higher risks in women who initiated HRT after age 60 or more than 10 years from menopause onset. Newer trials and observational studies using lower-dose, often transdermal estradiol and different progestogens suggest a more favorable benefit-risk profile in healthy women who are under 60 and within 10 years of menopause, particularly for the treatment of vasomotor symptoms and bone protection.

In parallel, the FDA and HHS have acknowledged that the original boxed warnings were based on data that did not adequately reflect current formulations, doses, or typical candidates for treatment and have moved to remove these broad warnings from product labeling while preserving more targeted risk information. These changes have helped normalize MHT as a reasonable option for appropriately screened women, rather than a therapy to be avoided.

Gaps in Training and Direct-to-Consumer Menopause Care

Despite accumulating data supporting the use of MHT in selected perimenopausal and postmenopausal women, most gynecologists and internists currently in practice trained after the WHI publications. Many clinicians report limited education in contemporary MHT prescribing, including choice of route, dose, and duration and strategies for evaluating benefit–risk in complex midlife patients.

As a result, perimenopausal women frequently struggle to find clinicians who feel comfortable discussing or prescribing hormone therapy, even when they have significant symptoms that impair quality of life. Into this gap, a number of virtual and direct-to-consumer menopause services have emerged, offering telehealth consultations and MHT prescribing outside traditional health-care systems. While these platforms may increase access, many women feel uneasy about receiving prescriptions from unfamiliar clinicians or online companies.

Mental health providers may be the first to hear about these symptoms. While most mental health providers do not prescribe MHT, we can play a crucial role in validating symptoms, providing current, balanced information about MHT, and supporting patients in shared decision-making with their gynecologist or primary care provider.

Current Guidelines from the Menopause Society 2022 Statement

The 2022 Hormone Therapy Position Statement of the North American Menopause Society provides a framework for when and how to consider MHT. Key points relevant to mental health providers include:

• MHT remains the most effective treatment for vasomotor symptoms (hot flashes, night sweats) and the genitourinary syndrome of menopause 
• MHT has been shown to prevent bone loss and fractures
• For most healthy, symptomatic women who are younger than 60 and within 10 years of menopause onset, the benefits of MHT outweigh the risks when therapy is individualized and periodically reassessed.
• Women with primary ovarian insufficiency or premature/early menopause are at higher risk of bone loss, cardiovascular disease, and cognitive or affective disorders related to prolonged estrogen deficiency; in these women, MHT is recommended at least until the average age of natural menopause, assuming no contraindications.
  
• Routine discontinuation of MHT at age 60–65 is not required; continuation beyond 65 can be considered for persistent vasomotor symptoms, quality-of-life concerns, or osteoporosis prevention after individualized counseling about benefits and risks.

These recommendations underscore that treatment should be personalized, with shared decision-making and ongoing evaluation of symptom control, side effects, and evolving health status.

Typical Preparations and Approaches

It is useful to be familiar with common MHT regimens so we can interpret what patients are taking and recognize when formulations or doses might interact with mood or anxiety symptoms. In current practice, many experts favor transdermal estradiol combined with an appropriate progestogen for women with a uterus, given data suggesting lower risk of venous thromboembolism and stroke compared with some oral regimens, especially in women with cardiometabolic risk factors.

Common systemic estrogen options include:

• Transdermal 17B-estradiol: patches (e.g., 25–100 mcg/day), gels, or sprays, often preferred for women with migraine, elevated triglycerides, or higher thrombotic risk.
  
• Oral 17B-estradiol or conjugated estrogens: once-daily dosing; some women prefer oral formulations, but they may have more hepatic first-pass effects and thus may affect levels of other medications.

For women with an intact uterus, endometrial protection with a progestogen is required:

• Oral micronized progesterone (e.g., 100–200 mg/day) is commonly used and may have a more favorable mood and metabolic profile than some synthetic progestins.
  
• Oral or intrauterine levonorgestrel or other progestins are alternatives; the levonorgestrel IUD can provide endometrial protection plus contraception.

Local (vaginal) estrogen therapies (creams, tablets, rings) are used for genitourinary symptoms and, at low doses, have minimal systemic absorption and do not generally require a progestogen. Non-estrogen options for vasomotor symptoms, including SSRIs, SNRIs, gabapentin, oxybutynin, and the neurokinin-3 receptor antagonist fezolinetant, remain important for women who prefer to avoid or have contraindications to MHT.

Important Contraindications and Cautions

Mental health providers should not be the sole decision-makers regarding MHT initiation, but it is helpful to be able to recognize and discuss major contraindications and situations warranting caution. Absolute or strong contraindications generally include:

• History of estrogen-dependent cancer (e.g., breast cancer, certain endometrial cancers), particularly when disease is active or recent.
  
• Unexplained vaginal bleeding.
  
• History of venous thromboembolism, stroke, or myocardial infarction is thought to be estrogen-related, especially in the absence of other mitigating factors.
  
• Known thrombophilia with high thrombotic risk.
  
• Active liver disease that significantly impairs estrogen metabolism.

Relative contraindications (requiring individualized risk-benefit assessment and often specialist input) include poorly controlled hypertension, significant hypertriglyceridemia, high baseline breast cancer risk, and complex cardiometabolic comorbidity. Many women with treated hypertension, hyperlipidemia, or stable migraine can use appropriately selected transdermal regimens, but these decisions should be made collaboratively with gynecology and primary care.

MHT in the Treatment of Perimenopausal Depression and Anxiety

A key clinical question for mental health providers is whether MHT should be considered as a treatment for depression and/or anxiety symptoms emerging in the menopausal transition. At present, MHT is not considered a first-line treatment for major depressive disorder or anxiety disorders in midlife women. However, a growing body of research suggests that estradiol may have antidepressant and anxiolytic effects in some perimenopausal women, especially when there is a clear temporal association between mood symptoms and hormonal fluctuations.

Several randomized and controlled studies have examined estradiol for perimenopausal depression, with most reporting meaningful benefits compared to placebo. In one randomized controlled trial of 50 perimenopausal women with moderate depression, 12 weeks of transdermal 17B-estradiol (100 mcg/day) led to remission in 68% of women receiving estradiol versus 20% receiving placebo, suggesting a robust antidepressant effect in this selected group.  More recent analyses also indicate that transdermal estradiol can reduce symptoms of anxiety in perimenopausal women, though this remains an emerging area of research.

Taken together, these data support the view that estradiol can be an effective treatment for perimenopausal depression in some women, particularly when depressive symptoms co-occur with significant vasomotor symptoms and other indicators of hormone sensitivity. However, the evidence base is still limited compared with standard antidepressant therapies, and most guidelines do not recommend MHT as a first-line treatment for major depression.

Clinical Scenarios Where MHT May Be Considered 

For mental health providers, it is helpful to consider MHT as a potential adjunctive or parallel intervention in specific clinical contexts, in collaboration with a clinician who prescribes menopause care:

• • Partial response to antidepressants: For women in the menopausal transition who have a partial response to an SSRI/SNRI or other antidepressant but continue to experience vasomotor symptoms, insomnia, and/or cognitive symptoms, adding MHT (assuming no contraindications) may improve residual physical symptoms and indirectly improve mood and overall level of functioning.
    
  • Non-response to antidepressants with clear hormonal timing: A trial of MHT may be reasonable after failure of or limited response to standard antidepressant, particularly in women with depressive symptoms that worsen in late perimenopause or following abrupt changes in ovarian hormone levels (e.g., after oophorectomy or chemotherapy-induced menopause).

• PMDD or Premenstrual Exacerbation of Mood or Anxiety Symptoms: In those who experience new onset or worsening of PMDD during the menopausal transition, hormone therapy may be used to suppress ovulation and can reduce premenstrual symptoms.

• Prevention of new-onset depression in high-risk women: A single trial in euthymic peri- and early postmenopausal women found that transdermal estradiol plus progesterone halved the incidence of new-onset depressive symptoms over 12 months compared with placebo, suggesting a preventive effect in some high-risk women.

In all of these scenarios, MHT should be considered only after careful evaluation of individual risk factors, discussion of alternatives, and collaboration with clinicians who manage menopause care. It is crucial to emphasize to patients that HRT is not a universal solution for depression but may play a useful role for some women as part of a broader treatment plan.

How We Approach MHT in Our Practice

In our clinic, we do not typically initiate or manage hormone therapy. However, we do provide guidance regarding the management of perimenopausal symptoms, including vasomotor symptoms, sleep disturbance, mood changes, anxiety and fatigue. This involves:

• Conducting a careful assessment of mood, anxiety, cognitive, and sleep symptoms, as well as vasomotor and genitourinary symptoms, menstrual history, and other medical comorbidities.
• Prospective daily charting of symptoms to help clarify the timing and pattern of symptoms, especially in women who are still menstruating.
  
• Prescribing evidence-based psychiatric treatments, including CBT, SSRIs/SNRIs, and other antidepressants as first-line interventions for major depressive and anxiety disorders.
  
• Identifying women whose symptoms appear closely linked to the menopausal transition and who might reasonably benefit from a discussion of HRT, particularly when vasomotor symptoms and sleep disturbance are prominent and when there has been an inadequate response to standard psychiatric treatments.
  
• Encouraging patients to discuss HRT with their gynecologist or primary care clinician and, when appropriate, referring to a menopause specialist for more complex cases or for women with significant medical comorbidity.

Resources for Clinicians and Patients

It can be helpful to share reputable resources with a patient’s gynecologist or primary care provider, as well as patient-friendly educational materials:

• The 2022 Hormone Therapy Position Statement of The North American Menopause Society: Evidence-based recommendations on indications, contraindications, and practical prescribing guidance.
• The Menopause Society Clinical Practice Tools and patient handouts at menopause.org, include information on vasomotor symptoms, genitourinary symptoms, and bone health.
• The 2023 Practitioner’s Toolkit for Managing Menopause from the International Menopause Society provides algorithms, tables on MHT choices, and practical points on counseling, follow-up, and monitoring.

These resources can facilitate informed, collaborative conversations about MHT and help ensure that women receive individualized, evidence-based care during the menopausal transition.

—Ruta Nonacs, MD PhD