The human body produces four types of estrogen: estradiol (E2), estrone (E1), estriol (E3), and estetrol (E4). Each one dominates during a different life stage, from reproductive years to pregnancy to menopause. They all start from the same raw material (cholesterol, converted through a chain of steps into androgens, then into estrogens by an enzyme called aromatase), but they differ significantly in potency, where they’re made, and what they do.
Estradiol (E2): The Strongest Estrogen
Estradiol is the most potent and abundant estrogen during the reproductive years. The ovaries are its primary factory, though smaller amounts come from fat tissue, bone, the brain, and blood vessel walls. Estradiol handles most of the heavy lifting: triggering the release of mature eggs each menstrual cycle, thickening the uterine lining to prepare for a potential pregnancy, and regulating the cycle itself.
Its influence extends well beyond reproduction. Estradiol helps maintain bone density, supports cognitive function, and promotes the production of nitric oxide, a molecule that keeps blood vessels flexible and open. These wide-ranging effects explain why so many body systems feel the impact when estradiol levels drop during menopause.
Estradiol levels fluctuate considerably across a single menstrual cycle. During the first half of the cycle (the follicular phase), levels typically range from about 20 to 350 pg/mL. They spike to 150 to 750 pg/mL around ovulation, then settle back to 30 to 450 pg/mL in the second half. Before menopause, estradiol exists at roughly a 3:2 ratio with estrone, meaning it’s the clearly dominant form.
Estrone (E1): The Menopause Estrogen
Estrone is a weaker estrogen that plays a supporting role during the reproductive years but becomes the body’s primary estrogen after menopause. Once the ovaries stop producing significant estradiol, fat tissue takes over as the main estrogen source. It does this by converting an androgen called androstenedione into estrone through aromatization, accounting for roughly a quarter of all circulating estrone in postmenopausal women.
Think of estrone as a storage form of estrogen. Your body can convert it into the more potent estradiol when needed, and vice versa. This interconversion acts as a buffer, helping maintain at least some estrogenic activity even when the ovaries have largely shut down production. Because estrone production depends partly on fat tissue, body composition influences how much estrone a postmenopausal person makes.
After menopause, the ratio flips: estrone becomes the dominant circulating estrogen, while estradiol drops to much lower levels. This shift matters because estrone is a weaker activator of estrogen receptors than estradiol. The body still has estrogen circulating, but it’s a less powerful version, which contributes to the bone loss, cardiovascular changes, and other effects associated with menopause.
Estriol (E3): The Pregnancy Estrogen
Estriol is produced in large quantities only during pregnancy. The placenta manufactures it using precursors supplied by the fetus, making it a unique collaboration between parent and baby. Outside of pregnancy, estriol levels are nearly undetectable.
During pregnancy, estriol helps the uterus grow to accommodate the developing fetus, increases the body’s sensitivity to other pregnancy hormones, and prepares the body for labor, delivery, and breastfeeding. It’s a relatively weak estrogen compared to estradiol, but the sheer volume produced during pregnancy compensates for that.
Estriol also serves as a clinical marker for fetal health. Providers typically measure estriol levels between weeks 15 and 20 of pregnancy as part of a triple or quad marker screening. Abnormally low estriol can signal problems with the placenta or indicate certain fetal conditions, including Down syndrome. Unusually high levels may also flag potential complications.
Estetrol (E4): The Fetal Estrogen
Estetrol is the most recently described natural estrogen. It’s produced exclusively by the fetal liver during pregnancy, making it the only estrogen that originates entirely from the fetus rather than the parent’s body or placenta. Like estriol, it’s essentially absent outside of pregnancy.
What makes estetrol particularly interesting is its selective behavior. It binds to estrogen receptors with at least 25-fold lower affinity than estradiol, yet it still delivers meaningful estrogenic effects in certain tissues, including the uterus, vaginal tissue, bone, and the cardiovascular and central nervous systems. At the same time, it has a notably low impact on the liver and on blood clotting factors. This selective profile caught the attention of pharmaceutical researchers.
Estetrol is now the estrogenic component of an approved combined oral contraceptive (paired with a progestin called drospirenone), available in Europe, the US, Canada, Australia, and other markets. It’s also in late-stage development as a menopausal hormone therapy. Its appeal is that neutral effect on blood clotting: traditional synthetic estrogens used in birth control pills increase the risk of blood clots, and estetrol appears to largely sidestep that problem.
How the Body Makes Estrogen
All estrogens begin as cholesterol. Through a cascade of enzymatic steps, cholesterol gets converted first into pregnenolone, then into androgens like androstenedione and testosterone. The final and most critical step is aromatization: the aromatase enzyme strips a carbon atom from these androgens and reshapes the molecule into an estrogen. Androstenedione becomes estrone. Testosterone becomes estradiol. A modified form of testosterone becomes estriol.
This process happens primarily in the ovaries during the reproductive years but also occurs in fat tissue, bone, the brain, and blood vessel walls. After menopause, these non-ovarian sites become the body’s only source of estrogen, which is why aromatase activity in fat tissue plays such a central role in postmenopausal estrogen levels.
Synthetic Estrogens in Medications
Beyond the four natural estrogens, synthetic versions are widely used in hormonal medications. The most common is ethinyl estradiol, the estrogen found in most combined birth control pills for decades. It’s a modified version of natural estradiol, engineered to survive digestion and maintain stable blood levels, something natural estradiol struggles with when taken orally.
That stability comes with trade-offs. When natural estradiol is taken by mouth, progestins in the pill accelerate its conversion back to the weaker estrone, which can cause irregular bleeding. Ethinyl estradiol resists this conversion, providing more reliable cycle control. However, its stronger impact on the liver increases the production of clotting factors, raising the risk of venous blood clots.
Newer contraceptive formulations have moved toward lower doses of ethinyl estradiol, and the introduction of estetrol as an alternative represents a shift toward estrogens that are gentler on the liver and clotting system. Bioidentical estradiol (chemically identical to what the body makes) is also used in some hormone therapies, particularly patches and gels that bypass the liver by delivering the hormone through the skin.