Perimenopause and menopause

Menopausal hormone replacement therapy

What is hormone replacement therapy?

Menopausal hormone replacement therapy replaces the hormones that the ovaries no longer produce in sufficient amounts. It is the most effective treatment for hot flashes, night sweats and many other symptoms, and at the same time it protects the bones. The decision is always made individually, after a discussion of the benefits and the risks.

What does the treatment consist of?

Estrogen is the main hormone of the treatment. It is given through the skin (patch, gel or spray) or by mouth. In many women, treatment through the skin is preferred, because it does not increase the risk of thrombosis and stroke, especially in women with a higher weight.

Progesterone is needed in every woman who has a womb, to protect the lining of the womb. It can be given as micronized progesterone (natural progesterone) by mouth. This does not increase the risk of thrombosis, often helps with sleep and, according to observational data, may have a smaller effect on the breast than synthetic progestins. It can also be given through a hormonal coil with levonorgestrel, which also provides contraception. Women without a womb usually need estrogen only (women with a history of endometriosis need combined hormone replacement therapy, even after removal of the womb).

Most women do not need testosterone. In selected cases of low sexual desire, when hormone replacement therapy alone is not enough, it can be considered. Testosterone as part of hormone replacement therapy is a new field of research. The indication is very specific and concerns only a small number of women. Even so, testosterone products are now prescribed far too often, without proof that the benefit outweighs the risks. In addition, long-term safety for the heart has not been proven.

It is important for women to understand that the aim of hormone replacement therapy is a better quality of life without putting future health at risk. For this reason, hormone replacement therapy should follow strict criteria and should not be guided by trends on social media and the internet.

Vaginal estrogens act locally on symptoms of the vagina and the urinary tract. They can be combined with systemic treatment and used for a long time, and in many cases even when systemic treatment is not allowed (newer studies show that they are safe even in women who have had breast cancer, with no increase in recurrence or mortality).

The regimens

In the perimenopause, while periods still occur, the cyclical regimen is usually used: estrogen every day and progesterone for 12 to 14 days a month, with a bleed every month. After the menopause, the continuous combined regimen is usually used, with estrogen and progesterone every day and no bleeding.

Hormone replacement therapy in the perimenopause can be especially demanding. The ovaries are still working at the same time, and this makes hormone levels go up and down. In addition, hormone replacement therapy is not a method of contraception. When hormone replacement therapy is the right treatment for a woman in the perimenopause, it is important that she receives detailed information about what the treatment can and cannot do in this phase.

The benefits

The treatment relieves symptoms effectively. It maintains bone density and lowers the risk of fractures for as long as it is taken. When it starts before the age of 60 or within ten years of the menopause, it does not increase cardiovascular risk and is linked to lower overall mortality. It does not increase the risk of diabetes, and there are signs that it lowers it. Risk factors such as high blood pressure are not in themselves a reason against treatment, as long as they are well controlled.

The timing of the start matters a lot. The period from the perimenopause until the age of 60, or until ten years after the menopause, is called the window of opportunity. According to the timing hypothesis, blood vessels and the brain respond differently to estrogen, depending on how long they have been without it. In blood vessels that are still healthy, estrogen has a protective effect. When atherosclerosis is already advanced, this benefit is lost.

A Cochrane review from 2015 showed that, when treatment starts within ten years of the menopause, overall mortality is about 30% lower and coronary heart disease about 48% less common. When treatment starts after the age of 60 or more than ten years after the menopause, there is no benefit for the heart. However, studies also show no negative effect on the heart. The risk of stroke rises by about 21%. The same applies to the brain. Starting close to the menopause does not harm brain function (KEEPS study), while starting after the age of 65 was linked to a higher risk of dementia (WHIMS study). Hormone replacement therapy is not given only to prevent heart disease or dementia. For a woman with symptoms, however, starting within the window of opportunity offers the greatest benefit with the lowest risk.

The risks in numbers

Heart: Of 1,000 women aged 50 to 54, about 9 will develop coronary heart disease within five years without treatment, and about 10 with treatment. The difference is not statistically significant.

Stroke: Of 1,000 women aged 50 to 54, about 3 will have a stroke within five years without treatment. With estrogen through the skin the number stays the same. With estrogen by mouth it rises by about 1.

Thrombosis: Estrogen by mouth increases the risk, mainly in the first year. Treatment through the skin at usual doses does not increase it.

Breast cancer: According to the European Menopause and Andropause Society (EMAS, 2026), most women will not develop breast cancer because of hormone replacement therapy. With estrogen alone (in women without a womb), the risk does not change or changes very little, and vaginal estrogens do not increase it. With combined treatment for five years, there are about 8 to 10 extra cases among 1,000 women aged 50 to 59. The risk rises with the length of treatment. It is slightly higher with the continuous regimen than with the cyclical one, and it depends on the progestogen: it is lower with progesterone and dydrogesterone. After treatment stops, the risk falls again over time. Combined treatment does not increase deaths from breast cancer, and estrogen alone may reduce them. For comparison, over the same period and at the same age, overweight after the menopause leads to about 4 extra cases among 1,000 women, obesity to about 10, and alcohol to 8 to 11.

Lining of the womb: Estrogen without progesterone in a woman with a womb increases the risk of cancer of the womb lining. Adding progesterone removes this risk.

Ovaries: A possible very small increase, about one additional case per 1,000 women.

When is it not given?

Hormone replacement therapy is generally not recommended for women with a history of breast cancer or another hormone-dependent cancer (see the next section), severe liver disease, or vaginal bleeding that has not been investigated. With a history of thrombosis or stroke, the decision is made individually, often with treatment through the skin and in cooperation with other specialists.

Can hormone replacement therapy be given after cancer?

Hormone replacement therapy is not forbidden after every cancer. The decision depends mainly on whether the tumor responds to hormones. ESHRE (2024) and the British societies for gynecological oncology and menopause (BGCS and BMS, 2024) divide cancers into three groups.

Recommended or possible. After cancer of the cervix, vulva or vagina, after lymphoma, leukemia or stem cell transplantation, and after germ cell tumors or borderline tumors of the ovaries, hormone replacement therapy does not increase the risk of recurrence. When the treatment caused an early menopause, the guidelines recommend hormone replacement therapy until the average age of natural menopause. The same applies to carriers of BRCA1 or BRCA2 mutations without breast cancer after risk-reducing removal of the ovaries. In these women, hormone replacement therapy until the age of natural menopause does not seem to increase the risk of breast cancer, and estrogen alone carries a lower risk than the combination with a progestogen.

Possible after individual assessment. In early-stage, low-risk cancer of the womb lining, a randomized trial with 1,236 women found recurrence in 2.3% of women on estrogen and in 1.9% on placebo, with no significant difference. In epithelial ovarian cancer, mainly high-grade serous cancer, hormone replacement therapy does not seem to cause harm. In a randomized trial with 150 women, overall survival was even better, and a 2020 Cochrane review found an about 29% lower risk of death, with low certainty. In melanoma, the data neither support nor rule out hormone replacement therapy.

Not recommended. After breast cancer and after hormone-dependent tumors of the womb and ovaries: endometrial stromal sarcoma, leiomyosarcoma of the womb, granulosa cell tumors, advanced low-grade serous ovarian cancer, and high-risk cancer of the womb lining with positive hormone receptors.

What about breast cancer?

In the randomized HABITS trial with 442 women, a new breast cancer event occurred in 39 of 221 women on hormone replacement therapy and in 17 of 221 women without it, over a median of 4 years. The risk was about 2.4 times higher, and the trial was stopped early. The Stockholm trial found no increase in the first 4 years. After about 11 years, however, cancer in the other breast was about 3.6 times more common in women on hormone replacement therapy. In the LIBERATE trial, tibolone increased recurrences by about 40%.

There are two gray zones. The first is breast cancer with negative hormone receptors. In the HABITS trial, the increase mainly concerned tumors with positive receptors, but there were too few women with negative receptors for a safe conclusion. The second is carcinoma in situ (DCIS), for which there are no randomized trials. For this reason, some experts consider hormone replacement therapy individually in these cases. There are, however, serious reasons for caution. A woman with a receptor-negative tumor can develop a new receptor-positive cancer in the other breast. And most cases of DCIS have positive hormone receptors.

The practice's approach is clear. After breast cancer of any type, including a receptor-negative tumor or DCIS, the practice does not give systemic hormone replacement therapy. There are evidence-based non-hormonal treatments for every symptom. Vaginal estrogen is a safe option, because studies show that estrogen levels in the body stay very low, within the postmenopausal range. Even so, the doctor discusses every use of vaginal estrogen with the oncologist, so that care fits each individual case. For example, the use of vaginal estrogen in a woman who takes anastrozole needs especially careful assessment. More in the article Iatrogenic menopause.

What a woman can expect

Side effects such as breast tenderness, fluid retention, bloating or headache are common in the first months and usually settle within three months. If they continue, the doctor adjusts the dose, the form of treatment or the type of hormone. Irregular bleeding is common in the first three months. If it appears later, it needs to be investigated.

The first check-up takes place three to four months after the start, and then every six months. At every visit, the doctor reviews whether the treatment is still the right one and talks about the screening tests (mammography, cervical smear).

How long can treatment continue?

There is no arbitrary limit of age or duration. Treatment continues as long as the benefits outweigh the risks, and the decision is reviewed at every visit. Treatment can be stopped gradually or at once. Stopping gradually reduces the return of symptoms in the short term, but in the long term the result is the same.

Newer studies show that hormone replacement therapy is also possible in women over 60. A large study of about 10 million women over 65 (Baik and colleagues, Menopause, 2024) found that estrogen alone at this age was linked to lower overall mortality and to a lower risk of breast, lung and bowel cancer. Combined treatment did not change mortality, but it was linked to a slightly higher risk of breast cancer, and this increase was smaller with low-dose estradiol through the skin. At this age, too, the decision is individual and depends on the woman's history and risks.

The practice's approach

Sources: NICE NG23 Menopause, 2024 update (with the decision aid “Incidence of medical conditions with and without HRT”), British Menopause Society / Women's Health Concern 2026, EMAS – Menopause Essentials 2026: Risk of breast cancer, International Menopause Society, Baik SH et al., Menopause 2024 (hormone replacement therapy after 65), Beste et al., Am J Obstet Gynecol 2025 (vaginal estrogen after breast cancer), Global Consensus Position Statement on the Use of Testosterone Therapy for Women (2019), Women's Health Initiative, European Commission (approvals of fezolinetant 2023 and elinzanetant 2025). Boardman HMG et al., Hormone therapy for preventing cardiovascular disease in post-menopausal women, Cochrane Database of Systematic Reviews 2015. Cauley JA et al., Effects of estrogen plus progestin on risk of fracture and bone mineral density (WHI), JAMA 2003. Shumaker SA et al., Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women (WHIMS), JAMA 2003. Gleason CE et al., Cognitive effects of hormone therapy in early postmenopausal women (KEEPS), 2024. ESHRE – Evidence-based guideline: premature ovarian insufficiency (Panay N et al., Human Reproduction Open 2024), HCP Toolkit 2024. Taylor A et al., Management of menopausal symptoms following treatment of gynaecological cancer, BGCS and BMS guidelines 2024. Barakat RR et al., Randomized double-blind trial of estrogen replacement therapy versus placebo in stage I or II endometrial cancer (GOG), Journal of Clinical Oncology 2006. Eeles RA et al., Adjuvant hormone therapy may improve survival in epithelial ovarian cancer (AHT), Journal of Clinical Oncology 2015. Saeaib N et al., Hormone replacement therapy after surgery for epithelial ovarian cancer, Cochrane Database of Systematic Reviews 2020. Holmberg L et al., Increased risk of recurrence after hormone replacement therapy in breast cancer survivors (HABITS), Journal of the National Cancer Institute 2008. Fahlén M et al., Hormone replacement therapy after breast cancer: 10 year follow up of the Stockholm randomised trial, European Journal of Cancer 2013. Kenemans P et al., Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms (LIBERATE), The Lancet Oncology 2009.