HRT vs SSRI for Perimenopause: Comparing Two Common Treatment Approaches

Two Very Different Approaches to the Same Problem

When perimenopause starts affecting your mood, sleep, and daily life, two types of treatment come up most often in clinical conversations: hormone replacement therapy, usually called HRT, and selective serotonin reuptake inhibitors, known as SSRIs or SNRIs.

These are not interchangeable treatments. They work through completely different mechanisms, address different aspects of perimenopause, and come with different benefits, risks, and considerations.

Understanding both options helps you have a more grounded conversation with your doctor rather than simply accepting the first recommendation offered.

How HRT Works

Hormone replacement therapy addresses perimenopause by replenishing the estrogen (and often progesterone) that your body is producing less consistently. Rather than managing the downstream effects of hormone fluctuation, HRT targets the fluctuation itself.

Estrogen affects dozens of systems in your body: your brain chemistry, your cardiovascular system, your bones, your skin, your joints, and your sleep architecture. When estrogen is stabilized through HRT, many perimenopausal symptoms improve because their hormonal driver has been addressed.

HRT comes in many forms: patches, gels, sprays, pills, and implants. For people with a uterus, progestogen is typically added to protect the uterine lining. The right type and dose are determined by your symptoms, health history, and individual hormone picture.

How SSRIs and SNRIs Work

SSRIs and SNRIs are medications originally developed for depression and anxiety. They work by increasing the availability of serotonin (and in the case of SNRIs, norepinephrine) in the brain, which influences mood regulation, emotional reactivity, and certain physical processes.

They do not replace estrogen or address the underlying hormonal fluctuations of perimenopause. What they can do is modify how the brain responds to those fluctuations, particularly in the areas of mood, anxiety, and even hot flashes.

SSRIs have an evidence base for reducing hot flash frequency and intensity, which is why they are sometimes prescribed as a non-hormonal option for people who cannot or prefer not to use HRT. They are also effective for mood-related symptoms that may accompany perimenopause.

What Each Treats Well

HRT tends to be more comprehensive in its effects on perimenopause symptoms. It addresses hot flashes and night sweats directly, often more effectively than SSRIs. It also supports sleep quality, vaginal health, bone density, joint comfort, skin elasticity, and cognitive function in ways that SSRIs do not.

For mood symptoms that are tied to hormone fluctuations, HRT often resolves them because it addresses the root cause. Many people report significant improvement in anxiety, irritability, and low mood from estrogen alone, particularly if these symptoms arrived alongside other perimenopausal changes.

SSRIs excel at treating mood disorders and anxiety that are more independent of hormonal cycles, or that persist even after hormonal support is optimized. They have a stronger evidence base for major depressive disorder and generalized anxiety disorder than HRT does. They are also a reasonable option for hot flashes in people who cannot use hormones.

Some people do best on both: HRT to address the physical and hormonal symptoms, and an SSRI or SNRI to address a mood condition that has its own roots.

Benefits and Limitations of Each

HRT benefits include broad symptom coverage, protection of bone density, cardiovascular benefits when started early in menopause, vaginal health support, and treatment of the root hormonal cause of many symptoms. Limitations include that not everyone is a candidate (certain health histories require careful evaluation), it requires a prescription and monitoring, and some people experience side effects during the adjustment period.

SSRI benefits include a well-established safety record for mood and anxiety treatment, usefulness for people who cannot take hormones, and some evidence for hot flash reduction. Limitations include that they do not address non-mood perimenopausal symptoms like vaginal dryness or bone density, they can cause sexual side effects, they take weeks to reach full effect, and stopping them requires a gradual taper.

Neither option is risk-free, and neither is right for everyone. The quality of the evidence and the breadth of benefits differ meaningfully between them for perimenopause specifically.

Who Is Most Suited to Each Option

HRT tends to be most suited to people whose primary symptoms are physical: hot flashes, night sweats, vaginal symptoms, joint pain, sleep disruption, and bone concerns. It is also well suited to people whose mood symptoms are clearly tied to hormonal fluctuations rather than an independent mood disorder.

SSRIs tend to be most suited to people who have a history of or current major depression or anxiety disorder, who have contraindications to estrogen, or who have tried HRT and found it insufficient for their mood symptoms.

For people who are unsure which applies to them, a thorough evaluation with a menopause-knowledgeable provider or a psychiatrist with hormonal health experience is the most useful first step.

The Conversation to Have With Your Doctor