Progesterone Cream: Is It Worth It?
Frederick R. Jelovsek MD, MS
"Two years ago, I watched a very convincing video by Dr. John Lee about the advisability of using progesterone cream to regulate the estrogen level in a woman's body. He maintains that he has established that progesterone cream use by his patients alleviated many of their menopause-related problems, and reversed or prevented bone loss, heart problems, and many other health problems for which HRT is normally recommended. I wonder if any research has been done by other physicians to prove or disprove his claims. " "I am 58 and I have been avoiding HRT due to a history of breast cancer in my family. I have been menopausal since a D & C a year and a half ago. I exercise vigorously most of the year, and believe I am in good physical condition. A recent bone density scan showed a slight decrease in bone density in my hip, although my spine was normal. I have been using progesterone cream for 2+ years. It has appeared to alleviate my (minor) menopause problems, but I wonder if there is any other medical evidence that the progesterone cream will keep me healthy into old age." Sue
This question often comes up because of the search for non-estrogen preventatives of many of the changes that take place in a woman's physiology after menopause. Dr Lee addresses the use of progesterone (natural progesterone and not synthetic progestins) cream as an alternative to estrogen both pre-menopausally and post-menopausally. Since you are asking about its use after menopause, let us confine our discussion to the postmenopausal use of progesterone cream. The scientific data which specifically address the use of progesterone cream applied to the skin are not very extensive but there is some work that has been done.
The main premises in the postmenopause that Dr Lee alleges, as best I can tell from reading his material, is that progesterone will build bone (and thus help prevent osteoporosis), relieve hot flashes, and help prevent the new onset of coronary artery disease.
Is the progesterone cream absorbed from the skin?
The doses that Dr Lee recommends for menopause is 15 mg/day for 25 days of the calendar month. He suggests being off for 5 or 6 days each month to allow the progesterone receptors not become desensitized by a constant dose of progesterone. He recommends the creams that contain 450-500 mg of progesterone per ounce, which is 1.6% by weight or 3% by volume. Using 1/4 teaspoon daily would provide about 20 mg/day. One scientific study using 64 mg a day on the skin showed a rise in salivary levels of progesterone but not in blood levels (1). Salivary levels reflect an accumulation in the body over time rather than an instant blood level. Another study looked at twice the recommended dose, 20 mg twice a day and they found a slight change in the blood level of a metabolite of progesterone but no change in FSH, estradiol or testosterone levels (2). This is important because if any positive effect of progesterone is because of metabolism to an estrogen substance, thereby negating the intent of using it in the first place, you would expect both FSH and testosterone levels to lessen somewhat which is what they do if estrogen is given.
Finally, a third study looking at absorption found that when 30 mg a day was given for two weeks, followed by 60 mg a day for two weeks, raised serum levels of progestone and it could be detected in the range of 1.6 to 3.3 ng/mL. In premenopausal women being treated for luteal phase defects, 100 mg a day of vaginal progesterone cream is needed to raise serum levels significantly (3).Thus the 20 mg a day recommended by Dr. Lee is a somewhat low dose compared to that needed to show a rise in blood levels.
Does progesterone cream prevent hot flashes and osteoporosis?
One controlled scientific trial which compared the 20 mg a day dose of progesterone cream recommended by Dr Lee to a placebo in 102 women after menopause found that the progesterone cream did improve hot flashes significantly (83% reduction vs 19% reduction) but neither placebo or the cream produced an improvement in bone density such as you would expect for estrogen (4). This was the only study I could find that directly examined the effect of progesterone cream on osteoporosis.
We have known for many years that estrogen actually causes an increase in bone density. When synthetic progestins are added to estrogen, they do not blunt this positive bone growth effect at all. In fact when HRT with both estrogen and progestin are given to frail, 75 year old women, there is still a net gain of bone density in the spine and hip within a year (4.3% and 1.7%) versus placebo (0.4% and -0.1%) (5). This is interesting because Dr Lee maintains that estrogens do not help the elderly retain bone as well as younger postmenopausal women. We know that medroxyprogestone acetate (Provera®), a synthetic progestin, when given alone does not prevent bone loss (6), although there is some suggestion that when it is added to estrogen, it enhances the positive bone accumulation effect of the estrogen (7). In animals, medroxyprogesterone acetate does not seem to prevent bone loss when used by itself (8), but I could not find natural progesterone studies on human bone loss at all other than the cited negative study above.
It is very difficult to prove or disprove whether progesterone cream could have some positive effect on bone loss. It may have a little effect, but certainly it is not as much preventative effect as etrogens. I would say that if osteoporosis or osteopenia is already present, then an established osteoporosis treatment such as alendronate (Fosamax®) or estrogen would be recommended.
Can progesterone cream prevent endometrial cancer when taken with estrogen?
In the woman who has not had a hysterectomy, there is concern about estrogen supplementation alone causing uterine cancer. Progestins and progesterone supplementation are recommended when postmenopausal estrogen is given to prevent stimulating the development of ovarian cancer. A legitimate question is whether using progesterone cream can prevent the proliferative effect on the lining of the uterus (endometrium). One study has shown that both skin applied progesterone cream (1.5% twice a day) as well as vaginally applied progesterone cream can neutralize this proliferative effect of estrogen on endometrium (9). The skin cream was also much preferred over vaginal application.
While this does not prove that progesterone cream can be used this way to add to estrogen and prevent endometrial cancer, it is very likely that it has this positive effect. Remember that we use transdermal skin patches containing both estrogen and progestin as hormone replacement therapy and assume that the skin absorption of the progestin will help prevent endometrial cancer if a uterus is still present. The above study is good evidence that progesterone cream probably has this same beneficial effect.
Will progesterone cream give me the heart benefit that estrogens do?
There many studies over the last 30+ years that estrogens used postmenopausally can decrease the new occurence of heart disease. It is thought to do this partially by causing a dilation effect on the heart blood vessels and by raising high density lipoproteins (HDL), the good cholesterol. Some synthetic progestins are known to constrict heart vessels so there is concern whether natural progesterone can do this also. Using a vaginal progesterone cream, one study has shown that unfortunately progesterone has a constricting effect on blood vessels (10).
In general, synthetic progestins have a blunting or blocking effect on the ability of estrogen to raise good cholesterol (HDL) but it does not block the bad cholesterol (LDL) lowering effect of estrogens; the net result of combined estrogen and progestin HRT is to lower total cholesterol (11). Micronized progesterone by mouth has this same general blunting effect (12) but in another study it did not blunt the estrogen induced HDL increase as much as the synthetic progestins did (13).
I would say that natural progesterone alone probably has a negative effect on heart health but that if you are taking estrogen, you get a more positive heart health effect with HRT using natural progestrone than you would taking most synthetic progestins. It is hard to tell, however, whether this is a major or a more minor heart health benefit.
In summary, the progesterone cream should be somewhat beneficial for the hot flashes of menopause but there is no evidence at the current time that would recommend it for an osteoporosis prevention agent or for any new heart disease prevention effect. While we have not discussed the effect of progesterone on vaginal dryness of menopause, a woman should keep in mind that progesterone alone may not improve vaginal dryness if it is a menopause problem.
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