Menopausal Hormone Therapy and Cancer
What is menopausal hormone therapy?
Menopausal hormone therapy (MHT)—also called postmenopausal hormone therapy and hormone replacement therapy—is sometimes used to replace the natural hormones estrogen and progesterone in a woman’s body during and after menopause, when levels of these hormones drop. Providers may recommend MHT to relieve common symptoms of menopause, such as hot flashes and vaginal dryness, and to address long-term biological changes, such as bone loss (osteoporosis), that result from declining levels of estrogen and progesterone.
Like most therapies, MHT has not only potential benefits but also possible harms. People should discuss the likely benefits and harms they might experience with their providers before deciding whether to use MHT and what form to use.
MHT usually consists of estrogen alone or estrogen plus progestin, a synthetic form of progesterone. The hormones used in MHT are approved by the U.S. Food and Drug Administration (FDA) and come from a variety of plants and animals or are made in a laboratory. The chemical structure of these hormones is similar to those of hormones produced by women’s bodies. MHT can be given in a variety of ways. When the goal is to treat hot flashes and other systemic symptoms or to prevent osteoporosis, it is usually given as a pill, but it can be also be given systemically through the skin (e.g., via a patch, gel, or spray) or via an implant. When the goal is to address genitourinary symptoms such as vaginal dryness, MHT (containing low-dose estrogen only) is applied directly in the vagina (as a cream or suppository).
Which form of MHT is used depends on whether a woman has a uterus. Because estrogen, when used alone (i.e., without progestin) for systemic MHT, is associated with an increased risk of endometrial cancer, estrogen is used alone only in women who have had a hysterectomy. Women who have a uterus—that is, who have not had a hysterectomy—are generally prescribed estrogen plus progestin for systemic MHT. Vaginal estrogen to treat genitourinary symptoms is prescribed regardless of hysterectomy status.
Non-FDA-approved hormone products, sometimes referred to as “bioidentical hormones,” are custom-mixed (or compounded) drugs that are sometimes sold without a prescription on the internet. Claims that these products are “safer” or more “natural” than FDA-approved hormonal products are not supported by credible scientific evidence. More information about these products can be found on FDA’s Menopause & Hormones: Common Questions fact sheet.
What are the health effects of menopausal hormone therapy?
- The WHI Estrogen-plus-Progestin Study, in which women with a uterus were randomly assigned to receive either a hormone pill containing both estrogen and progestin (Prempro) or a placebo. The median duration of treatment was 5.6 years.
- The WHI Estrogen-Alone Study, in which women without a uterus were randomly assigned to receive either a hormone pill containing estrogen alone (Premarin) or a placebo. The median duration of treatment was 7.2 years.
Both trials were stopped early (in 2002 and 2004, respectively), when it was determined that both types of therapy were associated with specific health risks.
Findings of follow-up studies of WHI participants and other studies have shown that MHT is associated with both potential benefits and potential harms (1).
Potential benefits of MHT include:
- relief of hot flashes, night sweats, vaginal dryness, and painful intercourse with systemic and local estrogen or systemic estrogen plus progestin for as long as MHT is taken
- lower risk of hip and vertebral fractures with systemic estrogen or estrogen plus progestin for as long as MHT is taken (2–5)
- lower risk of breast cancer with systemic estrogen (3, 5, 6)
- lower risk of death from breast cancer with systemic estrogen (6, 7)
Potential harms of systemic MHT include:
- increased risk of vaginal bleeding with estrogen plus progestin (8) that may require assessment by endometrial biopsy (because bleeding is a risk factor for uterine cancer)
- increased risk of urinary incontinence with both estrogen alone and estrogen plus progestin (2, 9)
- increased risk of dementia with both estrogen alone and estrogen plus progestin when taken by those 65 years or older (10–14)
- increased risk of stroke, blood clots, and heart attack with estrogen alone and estrogen plus progestin for as long as MHT is taken (2–5)
- increased risk of endometrial cancer in people with an intact uterus with estrogen alone
- increased risk of breast cancer with prior use of estrogen plus progestin for at least a decade after use is discontinued (6, 15, 16)
- increased breast density with estrogen plus progestin, making mammography less effective and also increasing breast cancer risk (17–20)
- increased risk of death from lung cancer with estrogen plus progestin (21)
Importantly, MHT is not associated with an increased risk of death from all causes (7).
Who should not take menopausal hormone therapy?
Women who have had breast cancer in the past are often advised to avoid MHT because some studies suggest that it may increase the risk of breast cancer recurrence (22, 23). However, other studies have not shown an increased risk. For example, a Danish cohort study of postmenopausal women treated for early-stage breast cancer showed no increased risk of recurrence or mortality associated with the use of vaginal or systemic MHT (24).
Many studies have also been done to investigate whether MHT is safe for women who have experienced premature or severe menopausal symptoms as a result of cancer treatments that reduce hormone levels. A 2020 clinical practice statement from the Society of Gynecologic Oncology concluded that the benefits of MHT are likely to outweigh the risks for most people with epithelial ovarian, early-stage endometrial, and cervical cancer as well as for people with BRCA1 or BRCA2 gene mutations or Lynch syndrome and no history of breast cancer (25). However, the statement recommended against the use of MHT in women with advanced endometrial cancer, uterine sarcoma, or endometrioid or low-grade serous ovarian cancer.
Women who are seeking relief from hot flashes and vaginal dryness should talk with their health care provider about whether to take MHT, the possible risks of using MHT, what formulation might be most appropriate for them, and possible alternative ways to address their symptoms. FDA advises women to use MHT for the shortest time and at the lowest dose possible to control menopausal symptoms.
Are there alternatives for women who choose not to take menopausal hormone therapy?
Women who are concerned about the changes that occur naturally with the decline in hormone production that occurs during menopause can make changes in their lifestyle and diet to reduce the risk of certain health effects. For example, eating foods that are rich in calcium and vitamin D or taking dietary supplements containing these nutrients may help to prevent osteoporosis.
Medications may be an option to reduce certain changes that come with menopause. For instance, three non-hormonal treatments are approved by the FDA to treat symptoms of menopause: fezolinetant (Veozah) and paroxetine (Brisdelle), to treat moderate to severe hot flashes associated with menopause, and ospemifene (Osphena), to treat moderate to severe pain with sexual activity due to menopause-associated vaginal changes. Other non-hormonal therapies suggested by the North America Menopause Society for relief of menopausal hot flashes include selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, oxybutynin, gabapentin, and cognitive behavioral therapy (26).
Some women seek relief from menopausal symptoms with complementary and alternative therapies. Some of these remedies contain phytoestrogens, which are estrogen-like compounds derived from plant-based sources such as soy products, whole-grain cereals, oilseeds (primarily flaxseed), legumes, or black cohosh. However, the North America Menopause Society does not recommend supplements, herbal remedies, or acupuncture for relief of hot flashes (26).
A 2016 systematic review and meta-analysis of randomized clinical trials of phytoestrogen-containing therapies found that some of these were associated with modest reductions in the frequency of hot flashes and vaginal dryness (27). According to the National Center for Complementary and Integrative Health, there is little information on the long-term safety of the use of natural products for menopausal symptoms, and some can have harmful side effects or interact with other drugs a woman may be taking.