Estrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal activity: estrone (E1), estradiol (E2), and estriol (E3). Estradiol, an estrane, is the most potent and prevalent. Another estrogen called estetrol (E4) is produced only during pregnancy.
Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of reproduction. It typically occurs between the ages of 45 and 55, although the exact timing can vary. Menopause is usually a natural change related to a decrease in circulating blood estrogen levels. It can occur earlier in those who smoke tobacco. Other causes include surgery that removes both ovaries, some types of chemotherapy, or anything that leads to a decrease in hormone levels. At the physiological level, menopause happens because of a decrease in the ovaries' production of the hormones estrogen and progesterone. While typically not needed, a diagnosis of menopause can be confirmed by measuring hormone levels in the blood or urine. Menopause is the opposite of menarche, the time when a girl's periods start.
A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a synthetic progestogen. Progestogens are used most commonly in hormonal birth control and menopausal hormone therapy. They can also be used in the treatment of gynecological conditions, to support fertility and pregnancy, to lower sex hormone levels for various purposes, and for other indications. Progestogens are used alone or in combination with estrogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of progestogens include natural or bioidentical progesterone as well as progestins such as medroxyprogesterone acetate and norethisterone.
Oophorectomy, historically also called ovariotomy, is the surgical removal of an ovary or ovaries. The surgery is also called ovariectomy, but this term is mostly used in reference to non-human animals, e.g. the surgical removal of ovaries from laboratory animals. Removal of the ovaries of females is the biological equivalent of castration of males; the term castration is only occasionally used in the medical literature to refer to oophorectomy of women. In veterinary medicine, the removal of ovaries and uterus is called ovariohysterectomy (spaying) and is a form of sterilization.
Estrone (E1), also spelled oestrone, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estriol. Estrone, as well as the other estrogens, are synthesized from cholesterol and secreted mainly from the gonads, though they can also be formed from adrenal androgens in adipose tissue. Relative to estradiol, both estrone and estriol have far weaker activity as estrogens. Estrone can be converted into estradiol, and serves mainly as a precursor or metabolic intermediate of estradiol. It is both a precursor and metabolite of estradiol.
Raloxifene, sold under the brand name Evista among others, is a medication used to prevent and treat osteoporosis in postmenopausal women and those on glucocorticoids. For osteoporosis it is less preferred than bisphosphonates. It is also used to reduce the risk of breast cancer in those at high risk. It is taken by mouth.
Estradiol acetate (EA), sold under the brand names Femtrace, Femring, and Menoring, is an estrogen medication which is used in hormone therapy for the treatment of menopausal symptoms in women. It is taken by mouth once daily or given as a vaginal ring once every three months.
Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and for use by injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen medication. It is used in hormone therapy for menopausal symptoms and low estrogen levels, hormone therapy for transgender people, and in hormonal birth control. It is also used in the treatment of prostate cancer. The medication is taken by mouth or by injection into muscle or fat once every 1 to 4 weeks.
Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk of cardiovascular disease, and has been linked to diseases like urinary tract infections and osteoporosis.
Tibolone, sold under the brand name Livial among others, is a medication which is used in menopausal hormone therapy and in the treatment of postmenopausal osteoporosis and endometriosis. The medication is available alone and is not formulated or used in combination with other medications. It is taken by mouth.
Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such as hot flashes, accelerated skin aging, vaginal dryness, decreased muscle mass, and complications such as osteoporosis, sexual dysfunction, and vaginal atrophy. They are mostly caused by low levels of female sex hormones that occur during menopause.
Atrophic vaginitis is inflammation of the vagina as a result of tissue thinning due to low estrogen levels. Symptoms may include pain with sex, vaginal itchiness or dryness, and an urge to urinate or burning with urination. It generally does not resolve without ongoing treatment. Complications may include urinary tract infections. Atrophic vaginitis as well as vulvovaginal atrophy, bladder and urethral dysfunctions are a group of conditions that constitute genitourinary syndrome of menopause (GSM). Diagnosis is typically based on symptoms.
Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen medication which is used in menopausal hormone therapy and for various other indications. It is a mixture of the sodium salts of estrogen conjugates found in horses, such as estrone sulfate and equilin sulfate. CEEs are available in the form of both natural preparations manufactured from the urine of pregnant mares and fully synthetic replications of the natural preparations. They are formulated both alone and in combination with progestins such as medroxyprogesterone acetate. CEEs are usually taken by mouth, but can also be given by application to the skin or vagina as a cream or by injection into a blood vessel or muscle.
Estradiol (E2) is a medication and naturally occurring steroid hormone. It is an estrogen and is used mainly in menopausal hormone therapy and to treat low sex hormone levels in women. It is also used in hormonal birth control for women, in feminizing hormone therapy for transgender women, and in the treatment of hormone-sensitive cancers like prostate cancer in men and breast cancer in women, among other uses. Estradiol can be taken by mouth, held and dissolved under the tongue, as a gel or patch that is applied to the skin, in through the vagina, by injection into muscle or fat, or through the use of an implant that is placed into fat, among other routes.
Progesterone (P4), sold under the brand name Prometrium among others, is a medication and naturally occurring steroid hormone. It is a progestogen and is used in combination with estrogens mainly in hormone therapy for menopausal symptoms and low sex hormone levels in women. It is also used in women to support pregnancy and fertility and to treat gynecological disorders. Progesterone can be taken by mouth, vaginally, and by injection into muscle or fat, among other routes. A progesterone vaginal ring and progesterone intrauterine device used for birth control also exist in some areas of the world.
An estrogen (E) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy, and as part of feminizing hormone therapy for transgender women. They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of estrogens include bioidentical estradiol, natural conjugated estrogens, synthetic steroidal estrogens like ethinylestradiol, and synthetic nonsteroidal estrogens like diethylstilbestrol. Estrogens are one of three types of sex hormone agonists, the others being androgens/anabolic steroids like testosterone and progestogens like progesterone.
The timing hypothesis, gap hypothesis, gap theory, or critical window hypothesisfor menopausal hormone therapy is a scientific theory that the benefits and risks of menopausal hormone therapy vary depending on the amount of time a woman has been in menopause upon initiation of treatment. More specifically, it is thought that hormone therapy may be protective against coronary heart disease in women who initiate it in early menopause but may be harmful in women who start it in late menopause. The timing hypothesis may also extend to risks of breast cancer and dementia with hormone therapy. It is thought that the increase in breast cancer risk may be greater in women who start hormone therapy in early menopause but may be lower or that even decreased risk of breast cancer may occur in women who start in late menopause. The influence of hormone therapy on depressive symptoms may additionally be influenced by menopausal stage, with significant benefit seen in perimenopausal women but not in postmenopausal women. The timing hypothesis is potentially able to resolve conflicting findings between large observational studies and randomized controlled trials on long-term health outcomes with menopausal hormone therapy.
The Estrogen in Venous Thromboembolism Trial (EVTET) was a randomized controlled trial (RCT) of menopausal hormone therapy in 140 postmenopausal women with previous history of venous thromboembolism (VTE). It was a double-blind RCT of the estrogen, oral estradiol 2 mg/day, plus the progestogen, norethisterone acetate (NETA) (n=71) 1 mg/day versus placebo (n=69). The results of the trial were published in 2000 and 2001. The incidence of VTE was 10.7% in the hormone therapy group and 2.3% in the placebo group, with all events occurring within 261 days after study inclusion. The difference did not reach statistical significance in the sequential analysis, but was statistically significant if the sequential design was ignored. Markers of coagulation were likewise increased by hormone therapy. As a result of the high incidence of VTE in the treatment group, the trial was terminated prematurely. The researchers concluded on the basis of their findings that menopausal hormone therapy should not be used in women with a previous history of VTE.
The Menopause, Estrogen and Venous Events (MEVE) study was a retrospective observational study of menopausal hormone therapy and venous thromboembolism (VTE) in postmenopausal women with a previous history of VTE. It found that transdermal estradiol was not associated with increased risk of VTE whereas oral estrogens were associated with a large increase in risk. The mean dose of transdermal estradiol in the study was 50 μg/day, although data on dose were missing for around 50% of women. Similarly, a small study found that transdermal estradiol did not influence coagulation in women with prior VTE. These findings are similar to studies in menopausal women without prior history of VTE which have found that transdermal estradiol has minimal influence on coagulation and is not associated with increased risk of VTE at doses of up to 100 μg/day. Menopausal hormone therapy guidelines have cited the MEVE study and recommended use of transdermal estradiol over oral estrogens in women at high risk for VTE. However, randomized controlled trials (RCTs) are still needed to definitively confirm findings that transdermal estradiol is safer than oral estrogens in terms of VTE risk.
