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What You Should Know about Progesterone

Progesterone is a hormone made by a woman's ovaries, adrenal gland, and, during pregnancy, the placenta. It is the most important of a group of steroid hormones called the progestogens. In reproductive age women, progesterone thickens the lining of the uterus in preparation for implantation of a fertilized egg. To build the lining, progesterone breaks down proteins. Progesterone increases body core temperature, which likely explains why reproductive age women are more likely to overheat during exercise during the luteal phase (last two weeks) of their menstrual cycle, when progesterone is highest. Progesterone levels continue to rise during pregnancy, which prevents ovulation during pregnancy. It also inhibits your body's inflammatory responses so that you don't attack your fertilized egg. Additionally, progesterone suppresses uterine contractions, which helps prevent preterm labor. Progesterone also prepares the breasts for feeding.

During menopause, progesterone levels decrease dramatically, which causes irregular menstrual periods in perimenopausal women, difficulty concentrating, mood changes, anxiety or depression, sleep disruption, and hot flashes. Menopausal women have a higher risk of ACL and MCL tears in their knees as well as shoulder injuries because progesterone stabilizes tendons and ligaments. Since progesterone provides pain relief by increasing your pain tolerance, menopausal women experience greater pain. Progesterone also decreases the rate of bone absorption and reduces loss of calcium in urine so menopausal women do not have these protective bone health advantages. Progesterone produces a calming, anti-anxiety effect in the brain and increases brain-derived neurotropic factor (BDNF), which is essential for learning and memory formation. When progesterone drops during menopause, women are more predisposed to sympathetic drive and anxiety. You'll recall that your sympathetic nervous system is a network of nerves that helps your body activate its "fight-or-flight" response. Your parasympathetic nervous system is the network of nerves that control your "rest-and-digest" processes, which controls your body when you feel calm and safe.

As mentioned previously, progestogens is a collective term that encompasses natural progesterone, dydrogesterone (a natural variant of progesterone), and a range of synthetic compounds designed to mimic the action of your body's own progesterone. Progestogens, like estrogens, are commercially produced by a process called semisynthesis in a lab: one process starts with a specific type of wild yam and the other process uses soybean oil as the starting material. A series of chemical reactions produce the desired progestogen. Progesterone for use in menopause hormone therapy (MHT) is micronized, which means it has a smaller diameter and is thus absorbed more readily by the body.

Women with a uterus require a progestogen (or a selective estrogen receptor modulator (SERM) to reduce the risk of endometrial cancer that occurs when taking estrogen alone. Both progestogens and SERMs block estrogen from building the uterine lining, which reduces irregular bleeding and risk. Oral (but not transdermal) micronized progesterone provides this endometrial protection. Progestogens have variable absorption through skin via creams, and gels because the structure of the molecule causes it to bind to subcutaneous fat so they are not recommended. An exception is the combination estrogen and progesterone patch (CombiPatch) which has been shown in clinical testing to protect the uterus.

Besides providing protective effects against estrogen for women with a uterus, progestogen-only drugs have been found to be effective in treating hot flashes and night sweats. Oral micronized progesterone also has a mildly sedating effect, which may help some women correct sleep disturbances associated with menopause. Given progesterone’s role in the brain in reducing anxiety, I also prescribe progestogens for mood changes (like anxiety or rage). Finally, progestogens are commonly prescribed to perimenopausal women to treat irregular menstrual bleeding. Micronized progesterone and dydrogesterone appear to have the lowest risks for cardiovascular, clotting, and breast cancer risks compared with other progestogens.

In summary, progesterone is an important hormone for reproductive age women. The decrease in progesterone during menopause can cause unwanted symptoms that can be mitigated by taking progesterone alone or with estrogen as part of MHT. Menopausal women usually can take progestogens safely. Women with a uterus must take enough to protect their uterus from endometrial cancer if they are taking estrogen. If you have a uterus and are taking estrogen but not a progestogen (or a SERM), see your doctor at once. If you are not using MHT because you should not (or don't want to) use estrogen, you can talk to your doctor about using a progestogen alone to help with irregular menstrual bleeding during perimenopause, as well as hot flashes, night sweats, mood disorders, and/or sleep disruptions.

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