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Hormone replacement therapy and perimenopause

Everything you need to know about hormone replacement therapy.

Top things to know

  • Hormone Replacement Therapy (HRT) is a treatment in which synthetic hormones are taken to alleviate the symptoms experienced during perimenopause and postmenopause.

  • HRT comes in two different forms: estrogen-only and combined estrogen and progestin. Both can be taken as pills, creams, patches, or other forms. 

  • Benefits of HRT include relief from hot flashes, night sweats, vaginal dryness, and protection against bone loss.

  • Risks include a higher chance of stroke, blood clots, endometrial cancer, and breast cancer.


Navigating perimenopause, which most women experience between the ages of 40 and 44 (1), can be challenging and confusing. Hormonal changes can cause symptoms like hot flashes, mood changes, and sleep disturbances (2,3). Hormone replacement therapy (HRT) may help treat these symptoms for some people (4). But like any medication, HRT has its benefits and risks (5)

The safety and benefits of HRT have been subject to a lot of ongoing research and debate. Attitudes towards HRT, and how it is prescribed, have changed significantly over the past two decades (6). HRT was once widely considered controversial, because early studies indicated a link between combined-HRT treatment and an increased risk of breast cancer. There was also thought to be a link between estrogen-only treatment and an increased risk of stroke (6). The good news? These studies have been debunked. Most experts now agree that HRT can benefit women who start treatment between the ages of 50 and 59, or within 10 years of menopause (6)

Even better? Studies have also found that starting HRT within the first four years of perimenopause can significantly reduce the risk of heart disease and can even extend life expectancy (7). The risks and benefits of HRT can vary depending on the age a person starts, and the individual themselves (8). For women aged 60 to 79, starting HRT did not show significant beneficial effects in previous studies (6).

What is HRT and how does it work?

Hormone Replacement Therapy (HRT) is a treatment in which a person takes synthetic estrogen and/or progestin, the synthetic form of the hormone progesterone. HRT replenishes the naturally declining levels of estrogen and progesterone which occur during perimenopause and menopause (5,9,10). This replenishment can alleviate the symptoms of hormonal changes (11) like irregular menstrual cycles (3), hot flashes (12), vaginal dryness (3), mood changes (2), and sleep disturbances (3).  

Perimenopause, the time leading up to menopause, can last anywhere from a few months up to 11 years. On average, it lasts around four to five years (13,14,15,16). Menopause is the point in time at which someone hasn’t had a period for a full year (5).  

The two main types of HRT are estrogen-only and combined estrogen and progestin (17). HRT can be administered in different forms, such as pills, patches, gels, or creams (17). Read on to learn more about each type. 

What are the different types of HRT?

Estrogen-only HRT

Estrogen is the primary hormone used in HRT (6). As the name implies, estrogen-only HRT treatment contains the hormone estrogen, without progestin. It’s commonly prescribed for people who have had a hysterectomy (18)

Estrogen-only HRT is available in two forms: 

  • Systemic estrogen therapy: A high dose of estrogen is released into the bloodstream and helps to manage various vasomotor symptoms, like hot flashes and night sweats (11). Systemic estrogen therapy can be taken in different forms, such as pills, patches, gels, and sprays (11).

  • Local estrogen therapy: This is generally prescribed for people experiencing genitourinary symptoms, like  vaginal dryness, burning, and pain during sex (19). It’s applied to the vagina through creams, tablets, suppositories, and rings and delivers small doses of estrogen directly to the vaginal tissue (20).   

Combined HRT (estrogen and progestin): 

Combined HRT includes both estrogen and progestin. 

Combined HRT is often prescribed to manage vasomotor and genitourinary symptoms, which happen due to reduced estrogen levels (3,21,22). These symptoms include vaginal dryness and urinary incontinence (7,21). Combined HRT can help stabilize hormone levels, reduce the intensity and frequency of hot flashes and night sweats, improve mood, and promote better sleep (7). Often, people who are already prescribed systemic estrogen therapy will also be prescribed combined HRT in order to reduce the risk of endometrial cancer from excess estrogen (11).

Combined HRT dosages depend on a person’s menstrual cycle. For those with ongoing periods, cyclical dosing (using different dosages during specific weeks of the menstrual cycle (23)) is often prescribed. For those who have stopped having a period, continuous dosing—without a break—is usually prescribed. (24). Continuous dosing is not appropriate for perimenopausal women (24).

What are the benefits of taking HRT? 

HRT can alleviate perimenopause and menopause symptoms and promote overall well-being. 

These benefits include: 

  • Reduction of hot flashes, poor sleep, night sweats, and irritability (2,7,11,25)

  • Relief from vaginal dryness (11)

  • Protection against bone loss, which helps to reduce the risk of osteoporosis and bone fractures (11,26,27)

  • Decreased risk of death from coronary heart disease in women who are younger than 60 (27). This effect is more pronounced in people who start estrogen-only treatment within 10 years before menopause (27).  

  • Decreased risk of colon and rectal cancers when treated with combined estrogen and progestin (11,27)

What are the risks of taking HRT?

HRT, like any medication, comes with certain risks. The risks vary depending on the type of HRT you take. 

  • Both combined HRT and estrogen-only HRT are associated with an increased risk of breast cancer. This becomes higher the longer one uses either treatment (5)

  • Both combined HRT and estrogen-only HRT are associated with a small increase in the chance of stroke (5). This risk decreases soon after you stop treatment (28).  

  • Both combined HRT and estrogen-only HRT are associated with a slightly higher risk of gallbladder disease. (5).

  • Both combined HRT and estrogen-only HRT are associated with a slight increase in the risk of heart attack (5). This risk can be influenced by age, pre-existing medical conditions, and the timing of HRT initiation (5). Those with heart disease or an increased risk of heart disease may face a higher chance of developing heart issues (27). This risk is particularly noticeable within the first two years of starting HRT (27).

  • Combined HRT and estrogen-only HRT taken in pill form are associated with a slightly increased risk of developing blood clots (27). This risk decreases with time (27). HRT administered via patch, gel, cream, or spray is associated with a lower risk of developing blood clots  (5,19,28).

  • Estrogen-only HRT is associated with an increased risk of endometrial cancer,  if one hasn't had a hysterectomy (5). On the other hand, combined HRT is associated with a lower risk of endometrial cancer (7,28).

Obesity, smoking, physical inactivity, genetics, advanced age, and a family history of blood clots or breast cancer may heighten complications from HRT for blood clots and breast cancer (6). Also, if you have a history of breast cancer, endometrial cancer, stroke, heart attack, blood clots, or liver disease, systemic HRT is generally not recommended (11). Lastly, if you’re pregnant or suspect you may be pregnant, stop taking HRT immediately and speak to your healthcare provider (11)

What are the side effects of HRT?

Common side effects of HRT include (11,29)

  • Breast tenderness 

  • Bloating

  • Changes in mood

  • Increases in blood pressure

  • Uterine bleeding or vaginal spotting

  • Headache

  • Change in sexual desire

  • Upset stomach

  • Change in menstrual flow

  • Swelling in hands, feet, or legs

If you’re taking HRT and notice that any of these symptoms are persistent or get worse, speak to your healthcare provider (29). Tracking your experiences with Clue can also be a helpful way to understand how HRT affects you and your symptom patterns. 


If you're experiencing bothersome perimenopausal symptoms, HRT may help; but it’s not suitable for everyone (4). Speak to your healthcare provider or OBGYN to determine if HRT is the right choice for you. It's a good idea to discuss your experiences, personal history, and family history with your healthcare provider and ask about potential risks and benefits based on your health history.

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