Summary
Estrogen is a female sex hormone that is produced in the ovaries and, to a lesser degree, in the adrenal glands and adipose tissues. It is essential for the development of primary and secondary sex characteristics, as well as function of the reproductive organs. Estrogen also plays a role in several other processes, including bone metabolism and liver function. While ovarian insufficiency, aromatase deficiency, and hyperprolactinemia result in pathologically low estrogen levels, a decrease in estrogen is a normal feature of menopause. Possible symptoms of estrogen deficiency include menopausal symptoms, vaginal and endometrial atrophy, and osteoporosis. Increased estrogen levels may also have adverse effects, including gynecomastia, thrombosis, and an increased risk of breast and endometrial cancer.
Biochemistry
Ovarian estrogen synthesis
Estrogen synthesis primarily takes place in the ovarian granulosa cells.
- LH stimulates androgen synthesis in ovarian theca cells.
- FSH stimulates conversion of androgens to estrogens.
- Conversion of androgens to estrogens is catalyzed by the aromatase enzyme.
Extra-ovarian estrogen synthesis [1]
Estrogen is also produced in other aromatase-containing tissues:
Estrogen types
There are three types of estrogen: estradiol, estrone, and estriol.
- Potency: estradiol > estrone > estriol
-
During pregnancy, estrogen concentration increases.
- Estradiol and estrone: 100-fold increase
- Estriol: 1000-fold increase (it is secreted by the placenta as unconjugated estriol and a marker of fetal health)
- When estrogen binds to its receptor in the cytoplasm, a hormone-receptor complex is formed that translocates to the nucleus.
Obesity increases the risk of postmenopausal breast cancer. It is hypothesized that this is due to estrogen production in adipose tissue. [2]
Measurement of unconjugated estriol (uE3 or free estriol) is part of the prenatal screening for fetal anomalies (i.e., triple screen test and quad screen test). Decreased levels are associated with Down syndrome, Edward syndrome, molar pregnancy, and fetal demise.
Effects
Estrogen is a steroid hormone that promotes female sexual development and stimulates the growth and maturation of primary and secondary sex characteristics.
Genitalia/sex characteristics
-
Uterus
- Endometrial proliferation
- ↑ Myometrial excitability
- Cervix [3]
- Vagina: proliferation of epithelium
- Pubis: hair growth
- Breast: breast growth
Extragenital tissue [4][5]
- Bones: ↑ Bone formation by inhibiting bone resorption (induces osteoclast apoptosis)
- Blood vessels: protective effect against atherosclerosis
- Blood clotting: ↑ Risk of thrombosis
- Kidneys: ↑ Water and sodium retention (may contribute to edema)
- Protein synthesis
- Adipose tissue: female distribution of adipose tissue
- Liver
Adverse effects
Adverse effects of estrogen can arise from high levels secondary to increased endogenous production or medication (e.g., hormone replacement therapy during menopause):
-
↑ Cancer risk
- Endometrial cancer
- Breast cancer [2][6]
- Thrombosis
- Spider nevi, gynecomastia, and testicular atrophy in individuals with cirrhosis
- Breast hypertrophy, gynecomastia (in men), galactorrhea
- Weight gain (edema)
- Liver toxicity [7]
- Nausea and vomiting
- Depressive moods
Although estrogen is a risk factor for the development of some types of cancer, it reduces the risk of colon cancer.
High estrogen levels increase the risk of thrombosis.
Hyperestrogenism
- Definition: a condition of increased circulating estrogen
-
Etiology
- ↑ Estrogen production (e.g., due to ovarian tumors, obesity)
- Excess estrogen supplementation (e.g., due to hormone replacement therapy)
- ↓ Metabolism and excretion of estrogens (e.g., due to chronic liver disease)
-
Clinical features
- Both sexes: palmar erythema, spider telangiectasias
- Men
- Gynecomastia
- Testicular atrophy
- Reduced libido
- Erectile dysfunction, infertility
- ↓ Body hair (e.g., loss of chest hair, female pattern of pubic hair distribution)
- Women
- Menstrual irregularities
- Enlargement of the breast and uterus
- Infertility
- ↑ Cancer risk (e.g., endometrial cancer)
Hypoestrogenism
- Definition: a condition of decreased circulating estrogen
-
Etiology
- Menopause
- Ovarian insufficiency: idiopathic or secondary to an underlying conditions (e.g., Turner syndrome, polycystic ovary syndrome)
- Congenital aromatase deficiency (↓ aromatase → ↑ androgensand ↓ estrogen)
- Hyperprolactinemia (e.g., in pituitary adenomas, hypothyroidism)
- GnRH agonists
-
Clinical features
- Hot flashes
- Headaches
- Reduced libido
- Breast atrophy
- ↓ Bone density and secondary osteoporosis
- Urogenital atrophy
- Dyspareunia