Why Is Estrogen Responsible for So Many Weird Perimenopause Symptoms?

Perimenopause and menopause cause a variety of seemingly unrelated symptoms. From hot flashes to vaginal atrophy to weight gain to mental health issues, menopause impacts many different domains in the body. If you’ve had experiences with hormone imbalances in the past (including horrible PMS symptoms), you may identify that these symptoms are hormonal. The question is, how are these hormones so widespread, and how do they work? While many hormones and neurotransmitters are responsible for these complex changes, the mastermind behind it all is estrogen. The sources are all linked, so you can read them for yourself.

There are four kinds of estrogen in the body: estradiol, estrone, estriol, and estetrol, with the latter two being produced primarily during pregnancy. Before menopause, estradiol is the dominant form of estrogen in the body. Estradiol is produced by immature eggs in the ovaries, and as these eggs are depleted over time, so too does the amount of estrogen produced. When estrogen levels deplete enough, your brain can send signals to these eggs to produce more estrogen, which can cause fluctuating spikes and dips in the amount of estrogen produced during early perimenopause. Eventually, the reserves of immature cells become exhausted and estradiol stops being produced in the ovaries. After this point, estrone, a less potent form of estrogen produced in fat tissue and the adrenal glands, becomes the primary form of estrogen in the body. Once menopause is complete, total estrogen levels will drop by up to 95%.

Estrogen receptors can be found in high concentration throughout the genitourinary system, including the vulva, vagina, clitoris, urethra, and lower portion of the bladder. In the presence of estrogen, these receptors stimulate blood flow and collagen production, which keeps these tissues thick, moist, and elastic. Once estrogen levels deplete, these tissues can atrophy, becoming thinner, less robust, and more prone to dryness. Atrophy of the bladder and urethra can cause pain during urination and urinary incontinence. Atrophy of the vaginal tissue can cause pain during sex and irritation. Atrophy of the vulva can cause irritation, itching, and pain. Even the clitoris can atrophy, leading to shrinking and receding of the clitoris and loss of sensation.

Estrogen also triggers the exfoliation of epithelial cells (the protective layer of cells on the outside of organs such as the vagina), which causes the release of glycogen. This glycogen gets converted into lactic acid, the same stuff that makes your muscles burn during heavy exercise, by bacteria called lactobacilli. Lactic acid production is what is responsible for the high acidity (low pH) of the vagina. When the vaginal pH increases due to low lactic acid production (which can also happen due to use of vaginal cleaning products or presence of semen) it becomes a better environment for yeast and harmful bacteria to grow, which increases the chance of bacterial vaginosis and urinary tract infections.

When the vaginal pH increases due to low lactic acid production it becomes a better environment for yeast and harmful bacteria to grow, which increases the chance of bacterial vaginosis and urinary tract infections.

Beyond the genitourinary tract, estrogen plays a significant role in regulating mood. You may already be familiar with the impacts of estrogen on mood if you experience the emotional side of premenstrual syndrome (PMS). Estrogen levels are highest in the few days before and during ovulation, and if fertilization does not take place, estrogen levels drop in the days after. That crash in estrogen that causes you to be moody, fatigued, and brain fogged before your period is what happens all the time during menopause and perimenopause. Estrogen receptors can be found in many regions of the brain, including the hippocampus (memory and learning), the prefrontal cortex (executive function and emotional regulation), and the amygdala (fear, emotional processing, and memory). In the absence of estrogen, these receptors become less active, leading to brain fog, impacted memory, depression, anxiety, fatigue, and insomnia.

Estrogen also has a direct impact on serotonin production and reuptake in the brain. Serotonin, the neurotransmitter associated with happiness and quality sleep, is a derivative of the amino acid tryptophan. The rate limiting step (the step which determines the overall timing of the conversion) in this process is the production of the intermediate tryptophan hydroxylase. The presence of estrogen increases the production of this crucial intermediate, which increases the production of serotonin in the body. The drop in estrogen associated with menopause therefore causes a decline in serotonin production, up to a 50% decrease. Additionally, estrogen prevents the generation of the protein which mops up excess serotonin in the brain, which means that less estrogen leads to less available serotonin.

Estrogen doesn’t only impact serotonin, however, the decrease in estrogen observed during perimenopause triggers the hypothalamus to release the stress hormone norepinephrine, which in turn causes a decrease in acetylcholine (sleep, learning, memory) and dopamine (motivation and pleasure). The impact of estrogen on the brain is even thought to explain why hot flashes occur. Although the exact mechanism for hot flashes is still unknown, one theory is that the increase in norepinephrine caused by a lack of estrogen dysregulates the body’s natural thermostat.

The seemingly unconnected symptoms of perimenopause and menopause, from a dry vagina to a foggy brain to a sudden hot flash, are not separate problems. They are different expressions of the same underlying shift.

There is still much to be investigated when it comes to the role of estrogen in the perimenopausal body, but one thing is increasingly clear: the seemingly unconnected symptoms of perimenopause and menopause, from a dry vagina to a foggy brain to a sudden hot flash, are not separate problems. They are different expressions of the same underlying shift, your body adjusting to life without its usual supply of estrogen. Understanding the connection doesn’t make the symptoms any easier to manage, but it does make them easier to anticipate, name, and advocate for. Treatment options exist along a spectrum, from targeted, lower-risk approaches such as topical lubricants and moisturizers or SSRIs, to systemic hormone therapy for those whose quality of life is more broadly affected. None of these options are one-size-fits-all, and none are without tradeoffs, but each represents a real, evidence-based way to reclaim comfort and function. The right approach will look different for every person, and finding it starts with learning about what is happening to your body, and talking to your provider armed with the knowledge to advocate for yourself.

If you’d rather have the short version than the full breakdown, we have a plain-language summary here.

The key sources behind this piece, for anyone who wants to read further:

• Mehta J, Kling JM, Manson JE. Genitourinary syndrome of menopause. StatPearls, 2024.
• Mahendroo M, Simpson ER. Molecular mechanisms of estrogen action in female genital tract development. Differentiation, 2021.
• Wasnik VB, Acharya N, Mohammad S. Genitourinary syndrome of menopause: a narrative review focusing on its effects on the sexual health and quality of life of women. Cureus, 2023.
• Amabebe E, Anumba DOC. The vaginal microenvironment: the physiologic role of lactobacilli. Frontiers in Medicine, 2018.
• Cho JM, Lee J, Ahn EM, Bae J. Beyond hot flashes: the role of estrogen receptors in menopausal mental health and cognitive decline. Brain Sciences, 2025.
• Amin Z, et al. Interactive effects of estrogen and serotonin on brain activation during working memory and affective processing in menopausal women. PMC, 2011.
• Bansal R, Aggarwal N. Menopausal hot flashes: a concise review. Journal of Midlife Health, 2019.
• Maki PM, Henderson VW. Cognitive changes after menopause: influence of estrogen. Current Opinion in Obstetrics and Gynecology, 2009.
• Skorupskaite K, Anderson RA. A new hope for women with vasomotor symptoms: neurokinin B antagonists. Journal of Clinical Medicine, 2025.

This article is for informational purposes only and does not constitute medical advice. Always consult your healthcare provider for personal medical guidance.