Topical progesterone creams ineffective against bone loss

Zosia Chustecka

May 27, 2004

May 27, 2004

Rio de Janeiro, Brazil — Topical progesterone creams have been touted as a "natural" alternative to hormone replacement therapy and have been widely advertised in women's magazines and over the internet as an alternative option for postmenopausal women. Among the many claims made for these products is that they can prevent the bone loss that occurs after the menopause, and some even claim that they can increase bone mineral density (BMD).

But they don't, Dr Gill Pearson (Southampton General Hospital, UK) told the recent World Congress on Osteoporosis. She reported a double-blind placebo-controlled study in which postmenopausal women using a topical progesterone cream (containing 40-80 mg progesterone) twice-daily over 2 years actually showed a fall in BMD levels [ 1 ].

"Despite strong marketing claims to the contrary, doctors should advise women not to use these progesterone creams as protection against osteoporosis," says Pearson.

Natural progesterone creams for the menopause

The use of natural progesterone creams by menopausal women has been promoted particularly strongly for many years by Dr John R Lee [ 2 ], who died recently. Author of several books aimed at the general public, including Natural Progesterone: The Roles of a Remarkable Hormone and What Your Doctor May Not Tell You About the Menopause, he also ran a website,, which continues to issue regular newsletters and information about the benefits of natural progesterone creams and where to obtain them. Lee's main arguments for using these products was that many of the symptoms of the menopause are due to dwindling progesterone, but this theory flies in the face of conventional medical thinking that the main culprit is estrogen deficiency.

Cream was well absorbed but didn't affect bone

The trial that Pearson reported enrolled 45 postmenopausal women aged 49-70 years and measured BMD at the lumbar spine at baseline and at 6, 12, and 24 months. In addition, the researchers carried out blood, saliva, and urine assays in order check that progesterone was being absorbed through the skin, and they measured biochemical markers to assess bone turnover (the urine NTX/creatinine ratio).

For the first year, one group used a topical progesterone cream (1.5% USP) containing 40 mg progesterone twice daily, while the other group used placebo. Both groups showed a decrease in mean lumbar spine BMD at 12 months, and there was no significant difference between the two.

Mean lumbar spine BMD at 12 months

Progesterone cream
P value
-1.38% (95% CI 2.50-0.26)
-2.58% (95% CI 4.41-0.75)

To download the table as a slide, click on slide logo at the bottom of this page.

During the second year, the trial became an open-label study. The first group doubled the dose and applied 80 mg progesterone twice daily, whereas the placebo group started using the cream, at 40 mg progesterone twice daily, and also took a vitamin and mineral supplement. Both groups again showed a decrease in BMD at 24 months.

At the same time, a parallel group of 15 postmenopausal women used transdermal continuous combined HRT (containing estradiol 50 ¿g and norethisterone 170 ¿g/day) throughout the study. This group of women showed an increase in BMD at 12 months of about 5.5% (95% CI 2.10-8.97) and a further increase at 24 months. In addition, this group showed a 35% decrease in bone turnover by the end of year 2, whereas the other two groups showed no significant change from baseline values over the course of the study.

Even though the progesterone cream was well absorbed, it did not prevent bone loss or increase bone mass in postmenopausal women, Pearson and colleagues concluded. She suggested that perhaps a different dose or formulation or delivery system would be effective, noting that animal studies have shown that progesterone stimulates bone formation.\


  1. Pearson GC, McCullough WL, Taylor PA et al. Topical natural progesterone cream effect on postmenopausal bone loss: a two-year double-blind, randomized, placebo-controlled trial. From IOF World Congress on Osteoporosis Osteoporosis International  2004; 15(suppl 1):abstract OC 

  2. Lee JR. Topical progesterone. Menopause 2003; 10(4):374-377  



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