What is estrogen therapy?
Estrogen therapy, also known as hormone replacement therapy, is a treatment for alleviating the symptoms caused by menopausal transition (when a woman’s ovaries reduce or stop producing estrogen and progesterone). Menopause is when a woman has no periods for one year.
Estrogen therapy is also used for protecting menopausal women against potential diseases that low estrogen levels may cause.
Estrogen therapy is most beneficial for women under 60 years of age or when started early in menopause, within 10 years from menopause. Hormone therapy is unsuitable for breast cancer survivors. For women with an intact uterus, estrogen is usually combined with a progestogen hormone to reduce the risk of uterine cancer.
What does estrogen do?
Estrogen and progesterone are steroid hormones naturally occurring in the body. Though commonly known as female sex hormones, males also have estrogen and progesterone in low levels.
Estrogen plays an important role in the development and regulation of the sexual and reproductive system. Estrogen also stimulates egg production (ovulation) by the ovaries. Apart from the reproductive system, estrogen has effects on almost the entire body including:
- Gastrointestinal system
- Urinary tract
- Organs such as:
- Blood vessels
The central nervous system functions such as:
The body produces three forms of estrogen:
- Estradiol: Produced by the ovary and predominant in premenopausal women.
- Estrone: Formed from estradiol in a chemical reaction predominant after menopause.
- Estriol: Secreted by the placenta during pregnancy, and also derived as a metabolite (waste product after processing) from estradiol and estrone.
Progesterone is a form of progestogen, another important hormone produced by the body. Progesterone prepares the uterus to receive the fertilized egg by thickening the uterine lining (endometrium), and supports pregnancy. Progestin is a synthetic progestogen used in the preparation of hormonal medications.
What happens during menopause?
Absence of menstruation for 12 consecutive months is defined as menopause, after all other reasons are ruled out. The median age for natural menopause is about 52 years. Menopausal transition may take up to three years. Menopause may also occur earlier due to reasons other than natural such as surgery, radiation or chemotherapy.
During menopausal transition, menstruation becomes irregular and the intervals increase. The ovarian function reduces and estrogen levels drop which give rise to early menopausal symptoms such as:
- Hot flashes and night sweats (vasomotor symptoms)
- Sleep disturbances and insomnia
- Mood changes
Many other conditions may mimic the vasomotor symptoms of menopause and must be ruled out with tests before starting hormone therapy. Post menopause, estrogen deficiency may lead to genitourinary syndrome of menopause (GSM) which may cause:
- Genital symptoms such as:
- Urinary symptoms such as:
Menopausal women are at higher risk for developing diseases such as:
What are the FDA-approved hormone therapies?
Currently hormone therapy is approved for the following:
- Relief for vasomotor symptoms in menopause
- Prevention of bone loss and reduction of fractures in menopausal women
- Prevention of bone loss and menopausal symptoms in women who have premature ovarian failure, underactive ovaries (hypogonadism) or have had their ovaries removed
- Treatment of genitourinary syndrome of menopause
Hormone therapies are individualized based on the individual’s conditions and symptoms. The therapy may consist of estrogen alone or a combination of estrogen and a progestogen. Following are the FDA-approved hormone therapies, which are administered in four forms:
Most oral tablets are taken once daily. The FDA-approved drugs include:
- Estrogen products
- Conjugated estrogens (Premarin)
- Synthetic conjugated estrogens (Cenestin, Enjuvia)
- Esterified estrogens (Menest)
- 17-beta-estradiol (Estrace)
- Estradiol acetate (Femtrace)
- Estropipate (Ortho-Est, Ogen)
Estrogen with SERMs
SERMs are selective estrogen receptor modulators, which act as both agonists and antagonists to estrogen. SERMS help estrogen bind with certain tissues like bone and help prevent bone loss, but block estrogen from binding to breast tissues and protect against breast cancer.
- Bazedoxifene (SERM) and conjugated estrogens (Duavee)
- Medroxyprogesterone acetate (Provera)
- Norethindrone (Micronor, Nor-QD)
- Norethindrone acetate (Aygestin)
- Norgestrel (Ovrette)
- Megestrol acetate (Megace)
- Progesterone capsules
- Progesterone in peanut oil, micronized (Prometrium)
Estrogen-progesterone combination products
- Conjugated estrogen/medroxyprogesterone acetate (Premphase)
- Conjugated estrogen/medroxyprogesterone acetate (Prempro)
- Ethinyl estradiol/norethindrone acetate (Femhrt)
- 17-beta-estradiol/norethindrone acetate (Activella)
- 17-beta-estradiol/drospirenone (Angeliq)
- 17-beta-estradiol/norgestimate (Prefest)
Skin patches may be prepared with only estrogen or a combination of estrogen and progesterone. Skin patches are placed on the lower stomach and replaced with new ones once or twice weekly.
- Estrogen-only formulations (17-beta-estradiol)
- Estrogen and progesterone combination
- CombiPatch (17-beta-estradiol and norethindrone acetate)
- Climara Pro (17-beta-estradiol and levonorgestrel)
Gels, topical creams and sprays
- Gels, creams and sprays are absorbed through the skin and applied on the arms or legs daily.
- EstroGel (gel)
- Elestrin (gel)
- Divigel (gel)
- Estrasorb (topical cream)
- Evamist (spray)
Vaginal products are applied directly in the vagina. Creams and tablets are applied one to three times a week. Vaginal rings are generally replaced every three months.
- 17-beta-estradiol (Estrace)
- Conjugated estrogens (Premarin)
- Vaginal tablets
- Estradiol hemihydrate (Vagifem)
- Vaginal rings
- 17-beta-estradiol (Estring)
- Estradiol acetate (Femring)
Intrauterine devices are inserted into the uterus. Intrauterine devices release measured hormone doses daily and last up to five years. The intrauterine device for menopausal symptoms is prepared with a progestin.
Bioidentical hormones are plant-derived compounds that have the same structure as human hormones. Bioidentical hormone therapy is a possible option for women seeking a “natural” product. The only FDA-approved bioidentical product is an oral soft-gel capsule Bijuva, prepared with 17-beta-estradiol and natural progestins.
What are the benefits of taking estrogen?
Estrogen therapy, with or without progesterone, is consistently effective in relieving menopausal symptoms. Estrogen therapy is also beneficial for preventing some estrogen deficiency symptoms.
The benefits of taking estrogen are clear in some of the conditions arising from menopause, but results are mixed in some. Following is an analysis of estrogen therapy benefits in menopause-related conditions:
- Vasomotor symptoms: Studies show that hormone therapy reduces the frequency and severity of hot flashes by 65% to 90%.
- Cardiovascular disease: Studies indicate that hormone therapy reduces the risk of cardiovascular disease and stroke in women younger than 59 or less than 10 years from menopause, but increases the risk in older women and those who are more than 10 years from menopause.
- Breast cancer: Hormone therapy is not recommended for breast cancer survivors. The risk for breast cancer may be more with a combination of estrogen with medroxyprogesterone acetate than estrogen-only therapy. Oral estrogen with bazedoxifene did not show increased risk for breast cancer in two years. Breast density may increase with hormone therapy.
- Genitourinary syndrome of menopause: Vaginal hormone products are useful in relieving genitourinary symptoms and may also prevent urinary tract and bladder infections.
- Prevention of bone loss: Conjugated estrogens with bazedoxifene reduces bone density loss and the risk of fracture in menopausal women. Hormone therapy is usually used only when vasomotor symptoms are also present, because other non-hormonal medications are available for osteoporosis.
- Cognition and quality of life: Hormone therapy, if started early, may reduce the risk of Alzheimer’s, but may increase the risk if started after 60 years of age or more than 10 years after menopause. Relief from menopausal symptoms can improve quality of life.
- Other benefits: Other potential benefits of hormone therapy include:
What are the possible risks and side effects of estrogen therapy?
On the whole, estrogen therapy’s benefits outweigh risks when initiated early in menopause, when the woman is relatively young. All estrogen therapies carry increased risks for certain conditions such as:
- Stroke due to venous thromboembolism (blood clots in the veins)
- Uterine hyperplasia (overgrowth of endometrial tissue)
- Estrogen therapies with progestin have additional risks such as:
- Breast cancer
- Cardiovascular disease
Common side effects of hormone therapy include:
Additional administration-specific risks include
Oral hormone therapy
- Irritation on the skin where patch is applied
- Topical applications may rub or wash off before being absorbed
Vaginal products and intrauterine devices
- Increased risk for endometrial cancer
- Not useful for prevention of hot flashes
Other potential risks of hormone therapy include:
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