HRT vs Antidepressants for Perimenopause Mood: What the Evidence Says

Why Perimenopause Affects Your Mood

Mood changes during perimenopause are among the most distressing and least talked-about symptoms. Fluctuating estrogen levels directly affect serotonin, dopamine, and norepinephrine, the brain chemicals that regulate how you feel. This means that irritability, low mood, anxiety, and weeping spells in your 40s or early 50s are not simply stress or a personal failing. They are a neurochemical response to hormonal change. When you go to your GP, you may be offered antidepressants, HRT, or a combination. Understanding what each does, and does not do, helps you have a more informed conversation about which direction suits you.

What HRT Does for Mood

Hormone replacement therapy works by restoring estrogen (and usually progesterone) to more stable levels. Because mood disruption in perimenopause is driven by hormonal fluctuation, HRT addresses the underlying cause rather than the symptoms alone. Clinical evidence, including guidance from the British Menopause Society and NICE, supports HRT as a first-line option for perimenopausal mood symptoms when those symptoms coincide with other hormonal signs such as hot flashes, night sweats, or irregular periods. Many women notice improved mood within weeks of starting HRT, alongside improvements in sleep quality, which itself has a large downstream effect on emotional resilience.

What Antidepressants Do for Mood

SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors) are effective for clinical depression and anxiety disorders. They are sometimes prescribed for perimenopausal women, particularly when HRT is contraindicated or declined. SSRIs and SNRIs also have a secondary benefit: they reduce hot flash frequency and severity in some women, which is why they are sometimes used as an alternative to HRT for vasomotor symptoms. However, if mood changes are rooted in hormonal flux rather than a primary depressive disorder, antidepressants may be less targeted. Some women also experience sexual side effects or emotional blunting on SSRIs, which can worsen quality of life during an already challenging transition.

When Antidepressants Are the Right Choice

Antidepressants are appropriate in several specific situations. If you have a personal or family history of depression or anxiety disorder that predates perimenopause, your mood symptoms may not be purely hormonal. If HRT is contraindicated due to certain hormone-sensitive cancers, blood clot history, or other factors, an SSRI or SNRI gives your GP a safe route to treating your symptoms. Antidepressants are also worth considering when low mood is severe or accompanied by suicidal ideation, where waiting for HRT to take effect is not safe. Your GP will assess all these factors before recommending a course of treatment.

Combination Approaches

Some women benefit from both HRT and an antidepressant, particularly if there is a pre-existing mental health condition alongside perimenopausal hormonal change. In other cases, HRT alone brings mood back to baseline and antidepressants can be tapered over time. There is no one-size-fits-all protocol. The key is regular review. If you start HRT and still feel low after three months, it is worth revisiting with your doctor rather than assuming HRT has failed. Dose adjustments, switching delivery methods, or adding progesterone can all make a meaningful difference. Similarly, if you are on an antidepressant and still have significant hot flashes or sleep disruption, raising the question of HRT is reasonable.

Tracking Symptoms to Support Your Appointment

One of the most useful things you can do before any appointment about mood is to bring a symptom log. Telling your doctor you have felt low for three months is less actionable than showing a pattern of low mood days clustered around your cycle, or a clear link between poor sleep nights and irritability the following day. Apps like PeriPlan let you log symptoms and track patterns over time so you have real data to share. This kind of record helps your doctor distinguish between perimenopausal hormonal mood change and a primary mood disorder, which directly influences whether HRT, an antidepressant, or both is the right starting point.

Questions to Ask Your Doctor