Perimenopause and HRT: Timing, After 60, and Breast Cancer Risk

Perimenopause, or the menopausal transition, is the run-up to the last period. Most women start it between 45 and 55, it can last several years, and menopause is confirmed after 12 months with no period. The average age of menopause in the US is 52 (National Institute on Aging: What is menopause?).

Hot flashes and night sweats are the hallmark symptoms; the Menopause Society cites one large US study in which up to 80% of women had them at some point during the transition (Menopause Society: Perimenopause).

Hormone therapy is the most effective treatment for hot flashes and night sweats (NAMS 2022 position statement; PMID: 35797481). Evidence: A (multiple randomized trials).

Perimenopause has two twists, per the Menopause Society:

• You can still get pregnant. Use birth control until a year after your final period if you don’t want a pregnancy.
• Standard menopause doses can cause breakthrough bleeding while you still cycle. Clinicians often use continuous combined hormonal birth control (pill, patch or ring) instead, which also covers contraception, or a levonorgestrel IUD plus estrogen.

If you have a uterus, estrogen needs a progestogen alongside it to protect the uterine lining (ACOG: Hormone therapy for menopause). Options compared: estrogen patch vs gel vs pill and micronized vs synthetic progesterone. If you want to see a clinician online, see perimenopause treatment online.

The Menopause Society’s 2022 position statement: for women younger than 60 or within 10 years of menopause onset, without contraindications, the benefit-risk ratio is favorable for treating bothersome symptoms and preventing bone loss. For women who start more than 10 years after menopause or after 60, it appears less favorable because of greater absolute risks of coronary heart disease, stroke, blood clots and dementia (PMID: 35797481). Evidence: B (randomized-trial subgroups plus observational data).

The Women’s Health Initiative investigators reached a similar conclusion in 2024: the WHI trials do not support hormone therapy to prevent heart disease or other chronic disease, but support starting it before 60 for bothersome symptoms in women without contraindications (Manson et al., JAMA 2024; PMID: 38691368).

In November 2025 the FDA asked makers of menopause hormone therapy to remove the cardiovascular, breast cancer and probable-dementia language from the boxed warning. For systemic products it asked them to add this timing guidance (consider starting for moderate to severe hot flashes in women under 60 or less than 10 years past menopause) while keeping the cardiovascular and breast cancer warnings in the body of the label (FDA).

There are two different questions here.

• Starting after 60: the absolute risks are higher, so the case is weaker (PMID: 35797481). It is a decision for a careful one-on-one review.
• Continuing past 60 or 65: there is no automatic stop age. The Menopause Society says there is no “right” time to stop (Menopause Society: Hormone therapy); its 2022 statement says longer use should be for documented reasons such as persistent hot flashes, with shared decision-making and periodic reevaluation (PMID: 35797481). ACOG advises reviewing the decision with your ob-gyn every year.

The FDA also asked for the probable-dementia warning to be removed from hormone therapy labels, noting that the WHI dementia studies enrolled women aged 65 to 79, much older than women who usually start hormone therapy (FDA).

It depends on the type. In the long-term follow-up of the two WHI randomized trials (more than 20 years, 27,347 women aged 50 to 79), Chlebowski et al., JAMA 2020 (PMID: 32721007) found:

Evidence: A (two large randomized trials), but only for the pills tested: conjugated equine estrogens, with or without medroxyprogesterone acetate. Other estrogens and progestogens were not tested in these trials.

The Menopause Society says breast cancer risk usually does not rise until after about 3 to 5 years of estrogen plus progestogen, or about 7 years of estrogen alone. ACOG describes the combined-therapy risk as small and advises women with a history of hormone-sensitive breast cancer to try nonhormonal treatments first.

ACOG lists a history of breast or endometrial cancer, stroke, heart attack, blood clots or liver disease as reasons systemic hormone therapy usually isn’t recommended, and it is not for use in pregnancy. Clot risk may be lower with transdermal estrogen (patch, gel or spray) than with pills, per the Menopause Society.

For those who can’t or don’t want to take hormones, the Menopause Society’s 2023 nonhormone statement recommends cognitive-behavioral therapy, clinical hypnosis, SSRIs/SNRIs, gabapentin and fezolinetant (Level I evidence), and oxybutynin; it does not recommend supplements or herbal remedies for hot flashes (PMID: 37252752).

Vaginal dryness alone often responds to low-dose vaginal estrogen; see vaginal estrogen safety. Hormone therapy also prevents bone loss; see bone health after 50. To compare clinicians, see menopause HRT online.