Estrogen is responsible for the appearance of secondary sex characteristics for females at puberty and for the maturation and maintenance of the reproductive organs in their mature functional state.
Endogenous estrogens play a unique role as potent inhibitors of atherosclerosis due to anti-inflammatory, antioxidative and vasodilator effects, inhibition of vascular smooth muscle cell growth and proliferation, as well as beneficial effects on lipid, glucose metabolism, and coagulation.
In the cardiovascular system, estrogens activate at least three different estrogen receptors, which either act as nuclear transcription factors regulating gene transcription, or induce rapid, non-genomic cellular signaling cascades.
After menopause circulating estrogen levels are reduced from greater than 120 pg per mL to around 18 pg per mL.
Because of the protective cardiovascular effects of endogenous estrogens, women are 8 to 10 years older than men when first diagnosed with obstructive coronary artery disease,
Estradiol levels fluctuate from 10 to 800 pg/mL in the premenopausal state, depending on the time of the cycle.
Estradiol levels are typically less than 30 pg/mL in the postmenopausal state.
Estrogen deprivation after menopause leads to increase in total body fat.
Estrogens protect women from visceral obesity, insulin resistance, non-alcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma.
After menopause circulating estradiol is derived from estrone, which is converted in adipose tissue from adrenal androstenedione.
Estrogen production in post menopausal women is derived from non-glandular sources, primarily from subcutaneous fat.
Estradiol is made in the ovary and is the most powerful estrogen, estrone is mostly made from adipose conversion of androstenedione and estrioll is the highest circulating estrogen.
Given intravenously increases factor V and IX, increases fibrinogen, increases platelet aggregation and decreases capillary permeability.
Estrogen stimulates growth hormone secretion.
Increases levels of procoagulant factors VII, IX, X, XII and XIII and reduced concentrations of anticoagulant factors protein S and antithrombin, resulting in a prothrombotic state.
Use during menopause improves climacteric symptoms such as hot flushes and sweating.
Most effective therapy for vasomotor symptoms.
Increases the risk of gallbladder disease.
The major steroid regulating bone resorption.
Estrogen suppresses T cell TNF production by regulating T cell differentiation and activity.
In the bone marrow, estrogen downregulates the proliferation of hematopoietic stem cells through an IL-7 dependent mechanism.
It may require 10 years of use to substantially reduce fracture risk.
A small amount of estrogen is produced by the metabolism of adrenal steroids by conversion to estradiol in peripheral fat tissue.
Known to be prothrombotic with high doses associated with myocardial infarction, stroke and venous thrombosis.
Estrogen is associated with increased risk of venous blood clots due to increased liver formation of vitamin K-dependent clotting factors.
Estrogens may have a roll in triggering the release of nitric oxide through estrogen receptors, improving overall endothelial function.
Estrogen has a time depended beneficial effect if administed early in menopause, because a woman’s arteries are likely to be relatively healthy early in menopause:suggesting nitric acid production by estrogen effect can improve endothelial function and cardiovascular risks.
Does not reduce the overall risk of further cardiac events in postmenopausal women who have survived a myocardial infarction.
Aromatase inhibitors markedly reduce estrogen levels in postmenopausal women by deactivating or inhibiting aromatase, the enzyme responsible for estrogen synthesis from androgens.
Conjugated equine estrogens used to relieve vasomotor symptoms of menopause is associated with about twice the risk of venous thrombosis compared with estradiol (Smith NL et al).
When estrogens are applied to the skin or vagina, there is a lower risk of blood clots, whereas when used orally, the risk of blood clots and pulmonary embolism is increased.