Oral:Replacement for Standard Progestins
Preventing or Treating
Osteoporosis; “Opposing” Estrogen
Progesterone is one of the two primary female hormones. As the name implies, progesterone prepares ("pro") the uterus for pregnancy (gestation). Progesterone works in tandem with
estrogen; indeed, if estrogen is taken as a medication without being balanced by progesterone (so called unopposed estrogen), there is an increased risk of uterine cancer.
However, progesterone is not well absorbed orally. For this reason, pharmaceutical manufacturers developed "progestins," substances similar to progesterone which are more easily absorbed. Most of the time, a woman prescribed "progesterone" is really being given a progestin. Two of the most commonly used progestins are medroxyprogesterone and norethindrone. However, it has
been suggested that actual progesterone may offer benefits over progestins, such as fewer side effects.
Progesterone can be absorbed through the skin to some extent, and some alternative practitioners have, for years, promoted the use of progesterone creams. Such progesterone creams are typically, but misleadingly, said to contain "natural" progesterone. This is an oddly chosen term, as the progesterone in these creams is actually produced in a laboratory, just like other synthetic hormones. To avoid confusion in this article, we will call progesterone "true" progesterone, or just "progesterone."
Besides creams, a special form of true progesterone that can be absorbed orally, micronized progesterone, has recently become available as a prescription drug.
Inconsistent evidence suggests that progesterone cream might help reduce menopausal symptoms. However, it does not appear to be strong enough to balance the effects of estrogen, thus reducing the risk of uterine cancer. (Oral micronized progesterone
strong enough for this purpose.) Contrary to numerous books and magazine articles, there is no more than weak, inconsistent evidence that progesterone cream offers any benefits for osteoporosis.
Progesterone is synthesized in the body and is not found in appreciable quantities in food. For use as a drug or dietary supplement, progesterone is synthesized from chemicals found in
Another aspect of the widespread misinformation involving progesterone cream is the concept that Mexican yam itself contains progesterone, or substances that the body can convert into progesterone. This is incorrect. Industrial chemists can convert a constituent of Mexican yam (diosgenin) into progesterone, but only by using chemical pathways not found in the body.
The usual dose of progesterone in cream form is 20 mg daily. Although this dose might decrease
menopausal hot flashes (see below), most studies found that even doses as high as 64 mg daily do not provide enough progesterone to protect the uterus from the effects of estrogen.2,20,21 However, one study found that use of micronized progesterone cream at 80 mg daily produced similar progesterone levels in the body as an oral dose of 200 mg daily;23
oral micronized progesterone taken at a dose of 200 to 400 mg daily is approximately as effective as the standard dosage of the more commonly used progestins.
Progesterone cream was widely promoted in the 1990s a treatment for
osteoporosis, on the basis of meaningless “studies” whose designs were too poor to establish anything at all.4-6 When properly designed studies were performed, the results were at best inconsistent.7,20
Studies conflict on whether progesterone cream can help hot flashes.7,20
study failed to find any improvements in mood or
general well-being in menopausal women using progesterone cream.20
Like progestins, oral progesterone protects the uterus from the stimulating effects of unopposed estrogen. However, standard doses of progesterone cream probably provide too little progesterone to serve for this purpose (see next section).
Despite widespread reporting that true progesterone is effective for treating or preventing osteoporosis, the evidence for such an effect is at best inconsistent.
This notion began with test tube and other preliminary studies suggesting that progesterone or progestins can stimulate the activity of cells that build bone.10,11 Subsequently, a poorly designed and uncontrolled study (really, a series of case histories from one physician's practice) purportedly demonstrated that progesterone cream can slow or even reverse osteoporosis.12-14
However, a 1-year, double-blind trial of 102 women given either progesterone cream (providing 20 mg progesterone daily) or placebo cream, along with calcium and multivitamins, found no evidence of any improvements in bone density attributable to progesterone.15 A smaller, short-term trial found that progesterone cream has no effect on bone metabolism.20
In contrast to these negative results, benefits
were seen in a small 2-year, double-blind, placebo-controlled study in which 22 women were given progesterone cream.8
(Interestingly, in this study, use of progesterone cream plus soy isoflavones produced inferior benefits to those of progesterone cream alone.) It is, therefore, at least possible that progesterone cream is helpful for osteoporosis if taken for a long enough period; however, more research is needed.
In the 1-year, double-blind trial of 102 women described above, use of progesterone cream was found to significantly reduce hot flashes and related symptoms.16 However, a slightly smaller 12-week, double-blind trial failed to find progesterone cream helpful for reducing menopausal symptoms.20
The authors of this second study point out that the first study was statistically flawed.
Unless you have had a hysterectomy, if you take estrogen you need to take progesterone too, or run the risk of uterine cancer. Two 12-week, double-blind studies enrolling a total of about 100 women found that progesterone cream (at doses up to 64 mg) did not have the required protective effect on the cells of the uterus.2,20
One study, however, did find benefit at dosages of either 15 or 40 mg daily.21 The explanation for these disparate results may lie in the results of two other studies, which suggest that progesterone cream is erratically absorbed.3,22
You will see progesterone is sold as a dietary supplement, but it is a
hormone, not a food.
Like progestins, true progesterone causes side effects. In one study, oral micronized progesterone at a dose of 400 mg per day was associated with dizziness, abdominal cramping, headache, breast pain, muscle pain, irritability, nausea, fatigue, diarrhea, and viral infections.17
Though progesterone is an over-the-counter product, it is important to periodically test blood levels of the hormone. Progesterone should only be used under the supervision of your doctor. You and your doctor can decide the best option for testing.
Leonetti HB, Longo S, Anasti JN. Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss.
Obstet Gynecol. 1999;94:225-228.
Wren BG, McFarland K, Edwards L. Micronised transdermal progesterone and endometrial response [letter].
Cooper A, Spencer C, Whitehead MI, et al. Systemic absorption of progesterone from Progest cream in postmenopausal women [letter].
Lee JR. Is natural progesterone the missing link in osteoporosis prevention and treatment?
Med Hypotheses. 1991;35:316-318.
Lee JR. Osteoporosis reversal with transdermal progesterone.
Lee JR. Osteoporosis reversal, the role of progesterone.
Int Clin Nutr Rev. 1990;10:384-391.
Lydeking-Olsen E, Beck-Jensen JE, Setchell KD, et al. Soymilk or progesterone for prevention of bone loss: a 2 year randomized, placebo-controlled trial.
Eur J Nutr. 2004 Apr 14. [Epub ahead of print]
Prior JC. Progesterone as a bone-trophic hormone.
Endocr Rev. 1990;11:386-398.
Verhaar HJ, Damen CA, Duursma SA, et al. A comparison of the action of progestins and estrogen on the growth and differentiation of normal adult human osteoblast-like cells in vitro.
Physicians' Desk Reference. 53rd ed. Montvale, NJ: Medical Economics; 1999:125.
Wren BG, Champion SM, Willetts K, et al. Transdermal progesterone and its effect on vasomotor symptoms, blood lipid levels, bone metabolic markers, moods, and quality of life for postmenopausal women.
Leonetti HB, Wilson KJ, Anasti JN. Topical progesterone cream has an antiproliferative effect on estrogen-stimulated endometrium.
Fertil Steril. 2003;79:221-222.
Burry KA, Patton PE, Hermsmeyer K. Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen.
Am J Obstet Gynecol. 1999;180(6 Pt 1):1504-1511.
Hermann AC, Nafziger AN, Victory J, et al. Over-the-counter progesterone cream produces significant drug exposure compared to a Food and Drug Administrationapproved oral progesterone product.
J Clin Pharmacol. 2005;45(6):614-619
Last reviewed December 2015 by EBSCO CAM Review Board
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