What is progesterone?
Like estrogen, which gets much more public attention, progesterone is a female sex hormone. Women produce it in the ovaries and adrenal glands, and during pregnancy in the placenta. With all the talk about estrogen and estrogen replacement therapies, progesterone is sometimes left behind as the forgotten female hormone.

What does progesterone do?
During the reproductive years, progesterone prepares the uterine lining (or womb) for pregnancy. Each month, progesterone levels rise following ovulation. Unless you become pregnant, the progesterone levels drop and trigger a monthly menstrual period. Progesterone can also play an important role in balancing out the effects of estrogen. If you have too much estrogen and not enough progesterone, your body can be thrown out of balance. During menopause this imbalance may lead to symptoms such as hot flashes, night sweats, insomnia, vaginal dryness, irritability and decreased sex drive. During the reproductive years, this imbalance may cause premenstrual complaints such as water retention, breast tenderness, migraines and mood swings.

Is progesterone safe?
Progesterone has been used in a number of clinical applications since 1940. Its early use was to assist women with infertility. Progesterone has NOT been linked to increased cancer risk. In fact, a large study conducted in France found that using bio-identical progesterone did not cause any increase in breast cancer, whereas use of synthetic progestins did result in a statistically significant increase in breast cancer risk¹. It is important to note that progesterone is often confused with progestins, which have been linked to increased cancer risk as noted in the Women's Health Initiative in addition to the French study. As with all hormones, progesterone should be considered carefully in concert with your physician or health care provider.

Why is there a warning label on some progesterone cream products sold at health food stores?
The state of California, under Proposition 65, requires warning labels on consumer products that contain ingredients "known to the state" as posing potential cancer risk. Women in Balance believes that placing a warning label on progesterone cream products is not warranted. We would like to educate consumers about how Proposition 65 came about.

What is California Proposition 65?
California¹s Safe Drinking Water and Toxic Enforcement Act of 1986, also known as Proposition 65 ("Prop 65"), contains a list of over 800 chemicals identified as carcinogens. Prop 65 mandates that warnings be given to consumers of products that contain certain chemicals identified by the state of California as hazardous. Progesterone was added to this list in 1988 based on summaries from the National Toxicology Program (NTP) and the International Agency for Research on Cancer (IARC). Both of these programs only evaluated progesterone given to animals already predisposed to cancer. Progesterone was then given to these high risk animals in very high doses. Also, these animals were given known carcinogens in addition to the high doses of progesterone.

The NTP's Tenth Report on Carcinogens even acknowledges that "no adequate human studies of the relationship between exposure to progesterone and human cancer have been reported." Progesterone is a naturally occurring hormone produced by all humans, unlike most of the chemicals listed in Prop 65, which are not naturally present in humans.We want to advise women that these studies were not human studies and no human studies using progesterone have been linked to cancer risk. In fact, a recent study from France presents solid research that progesterone reduces breast cancer risk.⁴ Women in Balance believes in the need for more education about the status of current research, and expansion of further research on the role hormones play in midlife health.

What is "natural" or "bio-identical" progesterone?
Progesterone is a hormone produced in the body. The term "natural" or "bio-identical" progesterone refers to progesterone that is molecularly identical to the progesterone that the human body produces.

"Natural" or "bio-identical" progesterone is formulated from a substance found in Mexican wild yams and other plants. These similar plant hormones are further modified in a laboratory to become identical in chemical structure to the progesterone produced in a woman's ovaries.

Is progestin the same thing as progesterone?
No. Although these terms are often used interchangeably, they do not mean the same thing. Progesterone refers to the hormone produced in the body, or produced from a plant source but still chemically identical to human progesterone. In contrast, progestin is a hormone that is synthetically produced and may differ in structure to progesterone. You may also have heard of progestogens. This is a general term that applies to the category of both natural and synthetic hormones that act like progesterone in the uterus. See the difference in the molecular structure depicted below.

How do synthetic progestins compare with bio-identical progesterone? Synthetic progestins do not always act the same in the body as natural progesterone. Synthetic progestins are broken down in the liver into a variety of metabolites, and while some of these bind to progesterone receptors and thus may mimic some of bio-identical progesterone's effects, others can bind to various types of steroid receptors throughout the body, causing side effects.² For example, while natural progesterone promotes and sustains pregnancy, synthetic progestins cannot be used during pregnancy due to the potential risk to the fetus because of their wider range of hormonal effects. Also, clinical trials comparing bio-identical progesterone with synthetic progestins are showing a significantly better safety profile for the bio-identical progesterone group; in one large trial (PEPI), the bio-identical progesterone group had a healthier blood lipid profile.³

What happens to progesterone during menopause?
As you approach menopause, progesterone is the first hormone to decrease, followed by fluctuating estrogen levels. This phase, called perimenopause, may start as early as your late thirties or early forties and last as long as ten years. Your periods may become more irregular. You may not ovulate some months, and thus not produce any progesterone. This may disrupt the estrogen/progesterone balance, causing a variety of symptoms such as bloating, breast tenderness, night sweats, anxiety, insomnia, headaches, and irritability.

After menopause, your ovaries cease to produce progesterone, but the body will continue to produce up to 40% of the levels of estrogen you produced before menopause. Of course, the level of production depends on the individual. Since progesterone affects numerous aspects of your health besides pregnancy and menstrual periods, you may experience other symptoms. For example, progesterone has a calming effect on the nervous system, thus a lower level of the hormone may contribute to increased night sweats, anxiety, insomnia, irritability or mood swings.

Women in Balance is a national, non-profit association of women, doctors, health care professionals, and national organizations dedicated to helping women achieve optimal health, wellness and hormone balance. Click here to go to the home page www.womeninbalance.org.

1. Stanczyk FZ. All progestins are not created equal. Steroids 2003; 68:879-90.
2. Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA 1995; 273(3):199-208. 3. Leonetti HB, Longo S, Anasti JN. Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol 1999; 94(2):225-8.
4. Fournier A, Berrino F, Riboli E, Avenel V, Clavel-Chapelon F. Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. Int J Cancer 2005; 114(3):448-54.