What is progesterone?
Progesterone is a female hormone important for the regulation of ovulation and menstruation. Progesterone is used to cause menstrual periods in women who have not yet reached menopause but are not having periods due to a lack of progesterone in the body. Progesterone is also used to prevent overgrowth in the lining of the uterus in postmenopausal women who are receiving estrogen hormone replacement therapy.

FAQ's About Progesterone Cream
by John R. Lee, M.D. and Virginia Hopkins

Q: What is progesterone?

A: Progesterone is a steroid hormone made by the corpus luteum of the ovary at ovulation, and in smaller amounts by the adrenal glands. Progesterone is manufactured in the body from the steroid hormone pregnenolone, and is a precursor to most of the other steroid hormones, including cortisol, androstenedione, the estrogens and testosterone. In a normally cycling female, the corpus luteum produces 20 to 30 mg of progesterone daily during the luteal phase of the menstrual cycle.

Q: Why do women need progesterone?

A: Progesterone is needed in hormone replacement therapy for menopausal women for many reasons, but one of its most important roles is to balance or oppose the effects of estrogen. Unopposed estrogen creates a strong risk for breast cancer and reproductive cancers. Estrogen levels drop only 40-60% at menopause, which is just enough to stop the menstrual cycle. But progesterone levels may drop to near zero in some women. Because progesterone is the precursor to so many other steroid hormones, its use can greatly enhance overall hormone balance after menopause. Progesterone also stimulates bone-building and thus helps protect against osteoporosis.

Q: Why not just use the progestin Provera as prescribed by most doctors?

A: Progesterone is preferable to the synthetic progestins such as Provera, because it is natural to the body and has no undesirable side effects when used as directed. If you have any doubts about how different progesterone is from the progestins, remember that the placenta produces 300-400 mg of progesterone daily during the last few months of pregnancy, so we know that such levels are safe for the developing baby. But progestins, even at fractions of this dose, can cause birth defects. The progestins also cause many other side effects, including partial loss of vision, breast cancer in test dogs, an increased risk of strokes, fluid retention, migraine headaches, asthma, cardiac irregularities and depression.

Q: What is estrogen dominance?

A: Dr. Lee has coined the term "estrogen dominance," to describe what happens when the normal ratio or balance of estrogen to progesterone is changed by excess estrogen or inadequate progesterone. Estrogen is a potent and potentially dangerous hormone when not balanced by adequate progesterone. Both women who have suffered from PMS and women who have suffered from menopausal symptoms, will recognize the hallmark symptoms of estrogen dominance: weight gain, bloating, mood swings, irritability, tender breasts, headaches, fatigue, depression, hypoglycemia, uterine fibroids, endometriosis, and fibrocystic breasts. Estrogen dominance is known to cause and/or contribute to cancer of the breast, ovary, endometrium (uterus), and prostate.

Q: Why would a premenopausal woman need progesterone cream?

A: In the ten to fifteen years before menopause, many women regularly have anovulatory cycles in which they make enough estrogen to create menstruation, but they don't make any progesterone, thus setting the stage for estrogen dominance. Using progesterone cream during anovulatory months can help prevent the symptoms of PMS. We now know that PMS can occur despite normal progesterone levels when stress is present. Stress increases cortisol production; cortisol blockades (or competes for) progesterone receptors. Additional progesterone is required to overcome this blockade, and stress management is important.

Q: What is progesterone made from?

A: The USP progesterone used for hormone replacement comes from plant fats and oils, usually a substance called diosgenin which is extracted from a very specific type of wild yam that grows in Mexico, or from soybeans. In the laboratory diosgenin is chemically synthesized into real human progesterone. The other human steroid hormones, including estrogen, testosterone, progesterone and the cortisones are also nearly always synthesized from diosgenin. Some companies are trying to sell diosgenin, which they label "wild yam extract" as a medicine or supplement, claiming that the body will then convert it into hormones as needed. While we know this can be done in the laboratory, there is no evidence that this conversion takes place in the human body.

Q: Where should I put the progesterone cream?

A: Because progesterone is very fat-soluble, it is easily absorbed through the skin. From subcutaneous fat, progesterone is absorbed into capillary blood. Thus absorption is best at all the skin sites where people blush: face, neck, chest, breasts, inner arms and palms of the hands.

Q: What is the recommended dosage of progesterone?

A: For premenopausal women the usual dose is 15-24 mg/day for 14 days before expected menses, stopping the day or so before menses. For postmenopausal women, the dose that often works well is 15 mg/day for 25 days of the calendar month.

Q: What amount of progesterone do you recommend in a cream?

A: Dr. Lee recommends the creams that contain 450-500 mg of progesterone per ounce, which is 1.6% by weight or 3% by volume. This means that about ¼ teaspoon daily would provide about 20 mg/day.

Q: How safe is progesterone cream?

A: During the third trimester of pregnancy, the placenta produces about 300 mg of progesterone daily, so we know that a one-time overdose of the cream is virtually impossible. If you used a whole jar at once it might make you sleepy. However, Dr. Lee recommends that women avoid using higher than the recommended dosage to avoid hormone imbalances. More is not better when it comes to hormone balance.

Q: Wouldn't it be easier to just take a progesterone pill?

A: Dr. Lee recommends the transdermal cream rather than oral progesterone, because some 80% to 90% of the oral dose is lost through the liver. Thus, at least 200 to 400 mg daily is needed orally to achieve a physiologic dose of 15 to 24 mg daily. Such high doses create undesirable metabolites and unnecessarily overload the liver.

Q: Where can I get more information on progesterone and natural hormone balance?

A: For a detailed explanation of women's hormone balance issues, a hormone balance program, as well as detailed descriptions of how to use natural progesterone, the following books by John R. Lee, M.D. are recommended:

Progesterone use in Transsexuals
The use of progesterone to augment breast development is controversial in physicians treating MTF transsexuals. When deciding on a hormone regimen, prescribers should remember that it is estrogen that causes the serious side effects, so the lowest effective dose should be used. The manufacturers of estrogen and progesterone products specify them for medical use in females and do not acknowledge their use for transsexuals, so there is little clinical data available regarding this usage.

Progesterone is the third and optional component of the MTF regimen. Medroxyprogesterone is available as Provera and Depo-Provera. Medroxyprogesterone is a weak antiandrogen, and testosterone suppression may be accomplished with lower doses of estrogen.

Medroxyprogesterone is less androgenic than norethindrone and orgestrel. Micronized Progesterone is advantageous because it has a more favorable side-effect profile (anxiety and irritability) than medroxyprogesterone. It is also less androgenic when higher progesterone doses are needed, but is more costly.
Micronized progesterone is available as Prometrium or in a generic form as Microgest.

Duphaston (Dydrogesterone) may be used as an alternative to medroxyprogesterone acetate. It is not metabolised into testosterone within the body, and is therefore free of the virilising effects which some patients experience from other progesterones. A typical pre-op (or early post-op) dose would be 20mg in two doses, reducing to a single dose of 10mg daily post-op. Crinone is another medication available and contains the female hormone progesterone.