Hormone Replacement Therapy (HRT) And Progesterone Cream
The research on hormone replacement therapy (HRT) and progesterone is not scientifically conclusive, but there is good reason for osteoporosis sufferers to pay attention to it.
A variety of small studies and a growing body of experience with natural progesterone are making themselves known to people seeking a natural remedy for osteoporosis.
As more people search for natural remedies for osteoporosis, progesterone therapy is attracting attention both from patients and doctors.
Here is a quick summary of current research results with more detail to follow:
- Women's Health Initiative (2002) found that hormone replacement therapy (HRT) increased bone density but also increased the risk of heart disease, breast cancer and strokes. (HRT consists of estrogen and synthetic progestin which is very different than the natural progesterone found in creams.)
- Dr. John Lee (1990) reported that 100 women increased their bone density by 3-5% annually over a three-year period by using 3% progesterone creams; calcium and vitamin supplements; and exercise.
- Researchers conducting a literature review (2009) concluded that that progesterone creams are more effective and pose less risk of breast cancer and cardiovascular disease than synthetic HRT.
- St. Luke's Hospital (1999) found that 102 women experienced no benefit from progesterone cream after 3 years.
- The Southampton Osteoporosis Research Unit (2001) reported that 53 menopausal women using progesterone cream continued to lose bone density throughout the two-year study period.
Interpreting The HRT Research
When assessing the research on hormone replacement therapy and progesterone, it is important to understand the difference between scientifically valid research and less rigorous studies.
A valid medical study will be double-blind and placebo-controlled. It must involve large sample sizes (often in the thousands); have few drop outs and continue over long periods-often three to eight years.
The findings should also report the number of people with fractures rather than the number of fractures. Research should ideally distinguish between the needs of women and men, as well as between pre- and post-menopausal women, because of the different hormone profiles of each of these groups.
As a result, serious mistakes can be made in research that claims to have met the highest standards.
This was apparent to everyone when the Women's Health Initiative (WHI) revealed that FDA-approved hormone replacement therapy (HRT) was causing breast cancer, heart attacks and strokes... thirty years after hormone treatment had become one of the most prescribed drugs in the United States.
So keeping in mind that neither medical research nor the FDA are infallible... what did the Women's Health Initiative say about hormone replacement therapy and progesterone?
And what does other research say about the use of natural progesterone for osteoporosis treatment?
Women's Health Initiative Study (2002)
The main elements of this randomized controlled trial are:
- 16,608 postmenopausal women aged 50-79 years
- Comparison of estrogen (equine) plus progestin vs placebo
- Study halted after 5.2 years due to unacceptable health risks
The interest in hormone replacement therapy and progesterone rose significantly after the Women's Health Initiative (WHI) reported that the use of hormone replacement therapy (HRT) was accompanied by an increased risk of breast cancer, heart attacks and strokes.
The specific study was called "Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women" and is worth at least a look-see.
The report also found that hormone replacement therapy had a beneficial effect on bone density.
- Overall, there was a 24% reduction in all fractures and a 33% reduction in hip fractures in women assigned to the estrogen and progestin group.
- Hip bone density increased 3.7% after 3 years of taking estrogen and progestin compared to 0.14% in the placebo group.
The report concluded that the overall risks of HRT outweighed the benefits of improved bone density and these findings were later reconfirmed in a larger national study done in the UK, known as the Million Women Study.
It is noteworthy that most of the progesterone in pharmaceutical hormone replacement therapy was the synthetic progestin. It has effects similar to progesterone but is quite different than the progesterone creams that are being used as natural remedies for osteoporosis treatment.
Research On HRT And Progesterone
Since the WHI report, there has been an eager search for ways to capture the bone building benefits of hormone replacement therapy without the associated risk of strokes, heart attacks and breast cancer.
Many people have looked to the recommendations of Dr. John Lee, the Harvard-trained physician who authored the popular book "What Your Doctor May Not Tell You About Menopause."
Doctor Lee had published research in 1990 which reported significant bone density improvements through the use of natural progesterone cream.
While the study did not meet the standard required for solid scientific research, it was very encouraging to people searching for an alternative to prescription hormone replacement therapy.
Dr. Lee's Osteoporosis Reversal Study (1990)
Key elements of the study (JR Lee. "Osteoporosis reversal; the role of progesterone." International Clinical Nutrition Review. 1990;10(3):384-91.):
- 100 women
- Age range: 38-83 years
- Study duration of 3 years
- Comparison of estrogen/progesterone and progesterone only
- Study included dietary changes, nutritional supplements and exercise
- Bone density measurement of 63 women included dual photon absorptiometry (DPA)
In this study, Dr. Lee reported that it was common to see a 10% increase in bone density in the first 6-12 months of hormone replacement therapy using natural progesterone.
He also reported an annual increase of three to five percent until bone density stabilized at the levels of a healthy 35-year-old woman.
The research also found that osteoporotic fractures dropped to zero and that there were no differences between estrogen/progesterone and progesterone only groups.
Subjective changes included increased libido, diminished hot flushes, reduced joint pain, and increased mobility and energy. No side effects were noted.
A recent literature review further supports the claim that hormone replacement therapy with progesterone cream is more effective and poses less risk than pharmaceutical HRT.
HRT Literature Review (January, 2009)
This review examined work that compared the effects of bioidentical and synthetic hormones including natural progesterone.. Researchers reviewed papers published within PubMed/MEDLINE, Google Scholar, and Cochrane databases.
The results indicated that bioidentical hormones are more efficacious than their synthetic and animal-derived counterparts and are associated with a lower risk of breast cancer and cardiovascular disease. They concluded that:
"Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT."
The bioidentical hormone debate comes down to this: Are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? See PMID: 19179815 for more details on this article in Postgrad Med. 2009 Jan;121(1):73-85.
Research Challenges To HRT With Progesterone
Dr. Lee's findings were not supported by a year-long study conducted at St. Luke's Hospital in Bethlehem, Pennsylvania in 1999 or by the Southampton Osteoporosis Research Unit in 2001.
These two studies were of similar size to Dr. Lee's but of shorter duration. Given the current understanding of the importance of vitamin and mineral support (and especially of Vitamin D) for osteoporosis treatment and prevention, the results of these studies cannot be considered conclusive as they did not include the recommended levels of vitamin D.
Transdermal Progesterone Cream (St. Luke's Hospital, 1999)
The key elements of this study were:
- 102 women within 5 years of menopause
- Study duration of one year
- Participants took 1,200 mg calcium and a daily multivitamin
- Comparison of placebo group and natural progesterone cream group
- Bone scans at beginning and end of study
Bone density improvements in the progesterone group were not superior to the placebo group after one year, but there was a significant improvement in vasomotor symptoms (hot flashes) in the progesterone group.
For more information, see "Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss." HB Leonetti, S Longo, JN Anasti.Department of Obstetric and Gynecology, St. Luke's Hospital, Bethlehem, Pennsylvania 18015, USA. Obstet Gynecol. 1999 Aug;94(2):225-8.
Southampton Osteoporosis Research Unit (2001)
The principal elements of the Southampton study were:
- Fifty-three healthy, post-menopausal women aged 52-65
- Study duration of 1-2 years
- Comparison of progesterone cream, HRT patch and placebo
- DEXA scans of bone density in the spine
- Healthy diet encouraged
- Vitamin and mineral supplements used by one progesterone group for one year
During the first year of the study at the UK Southampton Osteoporosis Research Unit, the progesterone group applied a quarter of a teaspoon of the progesterone cream twice a day (40 mg progesterone).
In the second year the progesterone cream group used half a teaspoon twice daily (80 mg progesterone) while the placebo group started to use a quarter of a teaspoon of the active cream twice a day.
This second group was also given a comprehensive vitamin and mineral supplement program. (Note: The amounts of progesterone used in this study exceeded the amounts recommended by Dr. Lee.)
A separate group of 14 women took hormone replacement therapy (HRT) using a skin patch.
All the women were encouraged to eat healthy diets high in dairy calcium, fruit and vegetables and to follow the general lifestyle advice recommended by the UK National Osteoporosis Society.
The study found that bone density in the HRT group increased by about 5%, while women using both the progesterone cream and the placebo lost around 2.5%. (Source: National Osteoporosis Society Online in the UK.
Warning About HRT With Progesterone And Soymilk
The importance of conducting further research on hormone replacement therapy and progesterone is underlined by the findings of the 2004 Soymilk And Transdermal Progesterone study whose key elements were:
- 89 postmenopausal, Caucasian women with established osteoporosis or at least 3 risk-factors for osteoporosis
- Four treatment groups (soymilk, progesterone, soy and progesterone, placebo)
- All groups received comparable calcium, minerals and vitamins
- DEXA bone density scans at baseline and after 2 years
This study found that daily intake of two glasses of soymilk containing 76 mg isoflavones prevents lumbar spine bone loss in postmenopausal women and progesterone cream also improved bone density.
But there was a loss of bone density when subjects used progesterone cream and also drank two glasses of soy milk a day.
For study details, see "Soymilk or progesterone for prevention of bone loss – a 2 year randomized, placebo-controlled trial." by Lydeking-Olsen E, Beck-Jensen JE, Setchell KD, Holm-Jensen T. Institute for Optimum Nutrition, Copenhagen K, Denmark. Eur J Nutr. 2004 Aug;43(4):246-57. Epub 2004 Apr 14.