Ovarian Hormone Support: Beyond Estradiol

Hormonal imbalances in women can occur through life stressors, PCOS, hypothalamic anovulation, hyperprolactinemia, perimenopause and menopause.  For many years ovarian hormone support for women has focused largely only on estrogen, mainly estradiol. Women have been offered oral contraceptives in the form of ethinyl estradiol combined with a synthetic progestin to help remedy hypothalamic anovulation and  PCOS. Women who are experiencing perimenopause and menopause are usually offered estradiol or conjugated estrogens. Historically, progestins and progesterone have been incorporated into hormone therapy and support regimens usually only to protect the uterus from unopposed estrogen and ensuing endometrial precancers and cancers which can develop. The contribution of  ovarian hormones to a women’s hormonal make-up extends far beyond this somewhat  simplistic view, and should be further investigated and hormone support regimens should be adjusted accordingly.

The major steroid hormones produced by the ovary include estrogen, progesterone and androgens. In addition to the development of female characteristics and reproduction, estrogens support healthy bone metabolism, nervous system function including cognitive function, cardiac disease prevention, and immunomodulation.  Estrogen deprivation is associated with lowered libido, altered mood and cognitive disturbances. Estrogen acts as a serotonin agonist. In the skeletal system, estrogen directly inhibits the function of osteoclasts and treatment with estrogen can increase the bone density of both the spine and the hip.  There is strong evidence that estrogen has a natural cardioprotective role.

The three forms of naturally occurring estrogen include estrone, 17β-estradiol, and estriol. Estrone and estradiol are the main biologically active estrogens secreted by the ovary; estradiol is the major estrogen produced by the premenopausal ovary and estriol is the major estrogen of pregnancy. Estrogens are also formed via the peripheral conversion of androgens into estrogens. This occurs in skin, muscle, and adipose tissue and in the endometrium. 

Progesterone plays a critical role in reproduction, and preparation of the uterine lining for reproduction. Largely, progesterone support has been studied and utilized to counter-balance the proliferative effects of estrogen on the uterine lining. Until recently, the major progestins employed in hormone support were synthetic as opposed to natural progesterone. It is very likely that this synthetic compounds will have differing effects on the body compared to more natural compounds. It is now being recognized that progesterone support may have other beneficial actions such as: neuroprotective effects in the CNS, cognitive effect, and immunomodulatory effects.  Emerging evidence suggests that some of these effects are influenced by specific hormone formulations, and that progesterone is more likely to be associated with positive outcomes than synthetic progestins.

Androgens in women are produced by the adrenal glands and ovaries. DHEA, androstenedione, and testosterone are produced by the ovary. These androgens are further converted outside the ovary to biologically active androgens such as testosterone and dihydrotestosterone (DHT). Testosterone receptors are found in numerous areas in women, including the brain. Testosterone replacement to physiologic levels in premenopausal and menopausal women may help with libido and sexual response, cardiovascular disease prevention, bone health, muscle tone including pelvic muscle tone, maintenance of ideal weight, mood and energy.

As with many health issues, hormone balance is highly individualized and complex and requires attention to multiple organ systems including the ovary, adrenal and thyroid. We should look beyond estradiol in isolation in women’s hormone balance.