What is hormone replacement therapy? Which women should use it, and when?

The postmenopausal hormone therapy guideline, relevant to many women and closely followed particularly because of noteworthy developments over the past 15 years, has been updated. This practice aims to reduce symptoms caused by declining female hormones after menopause and is called hormone replacement therapy (HRT) or hormone replacement treatment . The North American Menopause Society announced an update of its guideline previously published in 2012, incorporating women's health studies and new clinical trial results from the past 5 years. Before explaining the benefits and risks of menopausal hormone therapy, sharing some basic information will be useful.

There are three stages of criteria for natural menopause (cessation of menstruation):

• Perimenopause (or menopausal transition); starts with irregular periods and lasts 1-2 years.
• Menopause; begins 1 year (12 months) after the end of menstruation.
• Postmenopause; covers the period after menopause.

There are two basic types of hormone therapy:

• Estrogen-only therapy: Estrogen is the hormone that most relieves menopausal symptoms. Estrogen therapy is recommended for women whose uterus has been removed through hysterectomy (surgery).
• Combined estrogen plus progesterone therapy: For women with a uterus, progesterone is added to estrogen to protect against the increased risk of endometrial (uterine) cancer caused by estrogen alone.

Hormone replacement therapy is the most important treatment option for symptoms impairing many women's quality of life, such as hot flashes, palpitations, sweating, restlessness and vaginal dryness, and is also among the most effective treatments for preventing bone loss and fractures. However, its risks and side effects mean it is not given to all postmenopausal women. These risks vary according to therapy type ( whether progesterone is used ), dose, treatment starting time and duration.

Heart disease and osteoporosis increase after menopause, and estrogen deficiency was thought responsible, so hormone therapy was widely used preventively in postmenopausal women in the 1990s. However, a study in 2002 changed this understanding because estrogen used during menopause did not protect women against cardiovascular disease. Therefore, today, estrogen treatments are no longer given to menopausal women to prevent heart disease.

Benefits of hormone replacement therapy

Postmenopausal hormone therapies have been approved by the American Food and Drug Administration (FDA) for 4 situations. Accordingly, the FDA approved:

1. Distressing menopause-related symptoms impairing quality of life (such as hot flashes, palpitations and sweating)
2. Prevention of bone loss (also to reduce fractures)
3. Replacement of reduced estrogen for a certain period in women with nonfunctioning ovaries or surgically induced early menopause; to relieve bone loss, cognitive and mood impairment and other menopausal symptoms (in those without a condition precluding use)
4. Hormone therapy for symptoms involving female reproductive organs and urinary tracts (the genitourinary region), to improve genital anatomy, relieve vaginal dryness, burning and irritation, increase vaginal cells, maintain vaginal acidity, and reduce burning urination and urinary tract infections.

Other benefits of hormone therapy that improve quality of life include preserving sexual function, relieving sleep disturbances and improving sleep quality , reducing nervous tension and joint pain, and protecting drying, thinning and wrinkling skin and shedding hair.

Risks of hormone replacement therapy

Studies have shown that hormone therapy does not significantly change the risk of various diseases in healthy women. However, it is claimed to increase breast cancer, endometrial (uterine) cancer, vascular occlusion and gallbladder disease risk in women with a family history or personal predisposition. Breast cancer risk is claimed to increase with long-term hormonal treatment, but some studies claim it does not increase risk and even carries a risk similar to low physical activity or obesity . When a woman using hormone therapy develops breast cancer, she naturally immediately blames the therapy. However, breast cancer occurs in nearly one in every 8 women, and most women with breast cancer have no history of hormone therapy. Limited studies in patients with a family history of breast cancer and BRCA 1-2 gene mutations have shown that hormone therapy after removal of their ovaries did not increase breast cancer risk.

Other benefits of hormone therapy that improve uterine cancer the increasing effect becomes almost similar to that in healthy women after progesterone is added to estrogen. Endometrial biopsy should be performed when necessary in women with suspicious uterine thickening. Particularly those with a family cancer history or uterine thickening are advised to receive hormone replacement therapy under regular medical supervision. Hormone therapy has a favorable effect on large intestine (colorectal) cancer . Studies have shown that therapy begun particularly early in menopause reduces colon cancer incidence. Its effect on lung cancer is considered neutral.

It may increase the risk of vascular occlusion (thrombosis) and stroke (paralysis). The vascular occlusion risk, particularly high during the initial years of therapy started immediately after menopause, is claimed to decrease after the first year.

Accordingly, the 2017 (new) guideline generally states;

• The lowest dose providing relief should be used for the shortest duration to control menopausal symptoms.
• Women younger than 60 or starting therapy within the first 10 years of menopause are considered to have the greatest symptom-reducing benefit and safety regarding side effects. Particularly in this group, hormonal therapy has been observed to reduce heart disease and all-cause mortality risk.
• More than ten years after menopause begins, or in women over 60, hormone therapy risks may outweigh benefits because of significantly increased risk of cardiovascular harm, including coronary heart disease and venous thromboembolism (venous blockage), and dementia.
• Generally, insufficient evidence exists to prevent menopausal women older than 65 from receiving hormone therapy. As with other women, it should begin after careful assessment of all individual health benefits and risks.
• Suitable candidates entering early menopause through medicines or surgery before age 45 (especially age 40) are advised to start hormone therapy early and continue at least until age 52 to prevent cardiovascular disease, osteoporosis, mood disorders and sexual dysfunction.
• For uterine cancer patients whose uterus has been surgically removed and breast cancer patients (especially estrogen-receptor-sensitive) with persistent menopause-related hot flashes and palpitations, hormonal therapy is generally not recommended, but complementary therapies (such as acupuncture) may be used. Patients should discuss treatment options for these symptoms with their oncologists.

The main purpose of hormone therapy is to improve quality of life. It should therefore be fully individualized and based on a benefit-risk analysis. Regular medical follow-up afterward is also recommended, because periodic assessments may change hormonal treatment options or sometimes lead to discontinuation.