The Power of Progesterone

Women have it so easy don’t they? Forget high heels and more expensive dry cleaning bills. Those are mild compared to menarche, menopause, and about forty years of menstruation in between. Under the best of circumstances, the hormonal fluctuations that accompany these events can make life “interesting” for the women experiencing them as well as for the men who are close to them. (Not to mention their kids and coworkers!) But throw in the curveballs of modern life—poor diet, inadequate sleep, relentless psychological stress, and an environment rife with inescapable estrogenic compounds in manmade goods—and the effects on a woman’s hormones make towering amusement park roller coasters look like the kiddie teacup ride.

The modern functional medicine practitioner is likely to encounter female patients presenting with issues resulting from excess estrogen, inadequate progesterone, or both. Such imbalances may occur in women of reproductive age as well as post-menopausal women, and they can have a significant negative impact on quality of life. Among women of reproductive age, signs and symptoms of excess estrogen relative to progesterone include decreased sex drive, irregular or abnormal periods (including excessive bleeding), bloating, breast swelling and tenderness, mood swings (especially irritability and depression), weight gain, cold hands and feet, and premenstrual headaches.

While compounds such as calcium-d-glucarate and di-indolylmethane (DIM) are effective for reducing estrogen levels, other interventions may be needed to boost flagging progesterone levels. Younger women may benefit from exogenous progesterone for the treatment of dysfunctional uterine bleeding resulting from anovulatory cycles, and progesterone may also be beneficial for endometrial hyperplasia due to chronic unopposed estrogen.

Adequate progesterone (“pro-gestation”) is essential for a healthy full-term pregnancy, so pregnant women and those who are trying to conceive should ensure sufficient levels. In patients with a history of unexplained recurrent miscarriages, progesterone supplementation has been shown to slightly reduce the rate of subsequent miscarriages. Progesterone administration may also reduce the risk for preterm delivery and perinatal mortality among women with previous preterm deliveries. (In vitro data show progesterone inhibits fetal membrane weakening.)

Data are mixed when it comes to progesterone boosting fertility among women being treated with agents to stimulate fertility and/or undergoing intrauterine insemination (IUI). On the whole, there does seem to be a role for progesterone in increasing the likelihood of conception. A systematic review and meta-analysis found that luteal phase progesterone supplementation significantly increases live birth among women undergoing IUI when receiving gonadotropins for ovulation induction, but not among women receiving clomiphene citrate (CC). However, another study determined that progesterone does aid in conception in women taking CC compared to those not treated with progesterone. But yet another study showed that luteal phase progesterone administration significantly increased conception rate among women with PCOS who were treated with letrozole, but not with CC.

As for post-menopausal women, the natural decrease in progesterone levels that occurs with aging may result in hot flashes, mood swings, urinary incontinence, hair loss, vaginal dryness, poor concentration, uterine fibroids, loss of libido and an overall decline in health and quality of life. Additional symptoms include trouble sleeping, brain fog, and others that overlap with symptoms in younger women: breast tenderness, mood swings, water retention, and weight gain. Fortunately, many of these unpleasant and in some cases debilitating symptoms may be improved through restoration of healthy progesterone levels.

Data suggest that mean serum progesterone (and estradiol) concentrations are significantly lower among menopausal women reporting hot flashes compared to those not reporting hot flashes, and that higher levels of these hormones are associated with decreased odds of hot flashes. Micronized progesterone supplementation has been shown to significantly decrease moderate to severe vasomotor symptoms compared to placebo in early postmenopausal women, and it doesn’t cause a rebound increase in occurrence when treatment is stopped.

As with estrogen, there are both synthetic and natural bioidentical progesterone formulations available. Synthetic preparations often induce significant side effects, such as fatigue, fluid retention, lipid level alterations, dysphoria, hypercoagulant states, and increased androgenicity. Natural progesterone may present fewer side-effects while being equally if not more bioavailable than synthetic forms. Natural progesterone is obtained primarily from plants and can be administered via injection, through intravaginal or oral formulations, or applied topically and absorbed through the skin. Patients being treated with exogenous hormones should be monitored closely to ensure healthy hormone levels.