Measurement of estradiol (E2) is an integrated part of evaluating women's reproductive potential, including assessing infertility, oligomenorrhea, amenorrhea, and menopause. It also monitors ovulation induction and prepares for in vitro fertilization.
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Estradiol is a steroid hormone, one of the three main human estrogens, and the most active. In women of childbearing potential, estradiol is mainly produced by the follicles in the ovaries by the conversion (aromatization) of testosterone. In contrast, additional amounts of estradiol are made by converting testosterone in the peripheral tissues (excluding the ovaries, mainly the adrenal glands and adipose tissue). The placenta also produces estradiol. The estradiol concentration peaks in the middle of the menstrual cycle, signaling ovulation, followed by a rapid decrease, with a minor secondary increase during the luteal phase. In women of childbearing potential, estradiol has a daily (circadian) rhythm where peaks appear early in the morning. Peak time shifts later during the menstrual phase.
In women, estradiol is responsible for the development of secondary sex characteristics, enhancing breast growth and affecting body shape, bones, joints, and fat deposition. Estrogenic activity is mediated by the binding of estradiol to specific receptors, which can activate appropriate responses at the level of the cell nucleus to target organs and tissues. These tissues include the follicles, uterus, breast, vagina, urethra, hypothalamus, pituitary gland, and to a lesser extent, the liver and skin.
In men and pre-adolescent children, estradiol is mainly derived from androgen conversion. Small amounts of estradiol are produced in men in the testes, but there is no daily rhythm.
In addition to its role in sexual and reproductive function, estradiol affects other body parts, including the cardiovascular, brain, and immune systems. Estradiol has also been studied for its essential links with breast, ovarian, and endometrial cancers.
In women of childbearing potential, an increase in estradiol concerning progesterone, a condition known as "estrogen dominance," can explain many symptoms and signs, including endometrial hyperplasia, premenstrual syndrome, fibrocystic breast disease, and uterine fibroids. Women who are close to menopause may also experience symptoms of estrogen dominance, which include weight gain, fibrocystic breast disease and breast tenderness, uterine fibroids, irritability, and water retention. After the onset of menopause, low estradiol levels lead to hot flashes, night sweats, vaginal dryness, sleep disturbances, a head feeling heavy and "foggy" thinking, and osteopenia or osteoporosis. In men, higher estradiol levels relative to testosterone lead to feminization with gynecomastia and may lead to functional testosterone deficiency.
In the blood, only 1 to 15% of estradiol (usually 2-3%) is found in its unbound or biologically active form. The remaining estradiol binds to serum proteins, mainly sex hormone-binding globin (SHBG), and to a lesser extent to albumin. Unbound serum estradiol enters saliva through specific intracellular mechanisms. In saliva, most estradiol is not bound to proteins. The correlation of estradiol measurements in serum and saliva samples is high.
Estradiol is found in minimal amounts in saliva, about 1-5% of the total estradiol (protein-bound and free) circulating in the blood serum.
Measurements of hormones in saliva are an excellent choice because the sample collection is non-invasive and easy, without the possible complications and inconvenience of blood sampling, while ensuring the sensitivity and accuracy of the measurements.
