The 4 Types of Estrogen

1. Estrone (E1)

• A 17-ketone form of estradiol
• The dominant estrogen after menopause, produced mainly by peripheral conversion of androgens in adipose tissue
• Estrogenic activity roughly 10-30% that of estradiol
• Can be converted back to estradiol in tissues

2. Estradiol (E2 / 17β-Estradiol)

• The most potent and biologically active estrogen
• Predominates during the reproductive years, produced primarily by granulosa cells of the ovarian follicle
• Drives follicular development, endometrial proliferation, secondary sex characteristics, bone density, and cardiovascular protection
• Highest serum levels at the LH peak (ovulation)

3. Estriol (E3)

• The major estrogen of pregnancy - makes up more than 90% of estrogen in the urine of pregnant women
• Produced in the placenta from fetal adrenal precursors (primarily 16α-hydroxy-DHEAS, which undergoes 16α-hydroxylation mainly in the fetal liver)
• Has very low affinity for sex hormone-binding globulin (SHBG) and is cleared rapidly
• Maternal serum levels rise to 12-20 ng/mL by term
• Formerly used as a marker of fetoplacental function, but now largely abandoned due to poor specificity

4. Estetrol (E4)

• A 15α-hydroxy derivative of estriol, making it unique among the four
• Produced exclusively during pregnancy from fetal precursors - the fetal liver is the primary source
• Appears in maternal serum from around week 20 onwards and rises through term (as shown in the figure below)
• Has selective estrogen receptor modulator (SERM)-like properties - a synthetic form is now used in oral contraceptives (Nextstellis/Drovelis)
• Not present in non-pregnant women or men

Estrogen Levels During Pregnancy (from textbook Figure 10.5)

• E1 = post-menopause (One = done with ovulation)
• E2 = reproductive years (Two ovaries)
• E3 = pregnancy (Three = Third party = placenta)
• E4 = fetal (Four = Fetal)