Osteoporosis affects 10 million people in the United States, 80% of whom are women, and results in 1.3 million fractures every year. After menopause, the decrease in hormones such as progesterone and estrogens weakens the bones, increasing the risk of fractures. Here are the key points on the role of progesterone in bone health:
- Progesterone stimulates osteoblasts, which are responsible for bone formation, and can increase bone density by 15% over 3 years with a transdermal cream.
- Compared to estrogens, its action is complementary: estrogens reduce bone resorption, while progesterone promotes regeneration.
- Combined progesterone–estrogen treatments are more effective at improving bone density and reducing fractures.
- Natural progesterone is better tolerated than synthetic progestins, which may cause side effects.
Comparative Table: Progesterone vs Estrogens
| Hormone | Main Action | Effect on the bones |
|---|---|---|
| Progesterone | Bone formation | Stimulate the osteoblasts |
| Estrogens | Resorption reduction | Regulates calcium, reduces loss |
Recommendations:
- Consume 1,000 mg of calcium and 800–1,000 IU of vitamin D per day.
- Consider hormonal treatment before age 60 to maximize benefits.
- Prioritize a personalized approach under medical supervision.
Progesterone, in synergy with estrogens, represents a promising solution to prevent osteoporosis and protect your bones after menopause.
Osteoporosis, postmenopausal bone disease
Fundamental Functions of Progesterone in Bone Health
After explaining the key role of progesterone in bone regulation, let us examine its main mechanisms. Research indicates a direct interaction via specific receptors in the bones and an indirect influence on the action of glucocorticoids. These mechanisms allow us to better understand the processes of bone remodeling.
Bone Remodeling Process
Bone remodeling is a complex process in which progesterone plays a central role by stimulating the activity of osteoblasts, the cells responsible for bone formation. In laboratory tests, exposure to physiological concentrations of progesterone (6.4 × 10⁻⁷–10⁻⁹ M) for 7 days showed a 70% increase in alkaline phosphatase (ALP) activity. After 21 days, this activity is increased by a factor of 2.7.
However, supraphysiological concentrations (6,4 × 10⁻⁶ M) can produce the opposite effect, reducing ALP activity by 50%. These observations highlight the importance of hormonal balance in maintaining optimal bone health.
Comparative Effects of Progesterone and Estrogens
The effects of progesterone and estrogen on the bones are complementary but distinct:
| Hormone | Main Action | Mechanism |
|---|---|---|
| Progesterone | Bone formation | Stimulation of osteoblasts and cellular differentiation |
| Estrogens | Reduction of resorption | Calcium absorption and regulation via osteoprotegerin |
"If this anti-glucocorticoid effect of progesterone also applies to bones, then postmenopausal osteoporosis could be, in part, a disease related to a deficiency in progesterone." - Feldman et al.
Bone resorption markers, such as deoxypyridinoline (D-Pyr), vary throughout the hormonal cycle. They are higher during the follicular phase (dominated by estrogens) than during the luteal phase (characterized by a peak in progesterone).
Furthermore, progesterone stimulates the expression of the RUNX2 factor, which is essential for the differentiation of pre-osteoblasts. This action, combined with its ability to promote osteoblast maturation, makes it a key element in maintaining bone mass.
Research Results and Scientific Evidence
Key Results of the Studies
Clinical studies show a notable relationship between progesterone and bone health. For example, women with ovulatory disorders lose about 1% of vertebral bone mineral density (BMD) each year. During perimenopause, this loss averages -1.83 ± 4.49%, compared to -1.22 ± 3.14% at the onset of menopause.
The PEKNO study highlights a linear correlation (r = 0.7; p < 0.05) between the percentage of ovulatory cycles and the loss of BMD in pre- and perimenopausal women. This confirms the importance of ovulatory cycles in maintaining bone density.
| Treatment | Effect on the DMO | Annual Variation |
|---|---|---|
| Estrogens alone | Moderate increase | +1.3% |
| Estrogens + progestogens | Stronger increase | +1.7 % |
| Without treatment | Marked loss | –2,0 % |
To ensure the robustness of these results, rigorous methodologies have been implemented.
Methodology and Study Protocols
The conclusions are based on strict scientific protocols. A one-year randomized controlled study, conducted in a double-blind, placebo-controlled manner, for example evaluated cyclic medroxyprogesterone acetate (MPA), with or without calcium supplementation. Women with hypothalamic disturbances of the cycle or ovulation showed notable gains in vertebral BMD, ranging from +2 to +3% in the groups treated with cyclic MPA (F = 19,43; p = 0,0001).
The prospective E3N study, which followed 80,000 French women over eight years, revealed that micronized progesterone, unlike synthetic progestins, is better tolerated when combined with estrogens.
Furthermore, a meta-analysis of randomized clinical trials showed that the combination of conjugated equine estrogens and MPA results in a significantly greater annual increase in BMD (+0.68%; 95% CI: 0.38–0.97%) (p = 0.00001) compared to conjugated estrogens alone. These data reinforce the idea that progesterone plays a key role in treatments aimed at preserving bone mass.
Natural vs. Synthetic Hormonal Options
Effects on Bone Density
Natural progesterone and synthetic progestogens do not have the same impact on bone health. For example, Dr. John R. Lee's work shows an average increase of 15% in bone density in postmenopausal women using a transdermal progesterone cream for 3 years.
Treatments combining estrogens and synthetic progestins yield varied results. Here are the variations observed in bone mineral density (BMD) at the level of the L2-L4 vertebrae after two years:
| Type of treatment | Variation of the DMO (L2-L4) |
|---|---|
| Estrogens (E2) only | +2 to +4 % |
| E2 + MPA (medroxyprogesterone acetate) | +2 to +4 % |
| Micronized progesterone | Decline |
| NET (norethisterone) | Stable |
| Without treatment | -5% on average |
Security Considerations
These results also raise questions about the risks associated with each hormonal option. For example, DMPA (depot medroxyprogesterone acetate), a synthetic progestin, is linked to significant concerns. The FDA advises against its prolonged use, beyond two years. Here are some notable differences between natural and synthetic options:
-
Micronized natural progesterone:
- Generally better tolerated
- Lower impact on mood
-
Synthetic progestins:
- Higher risk of bone loss, especially in young women
- Frequent side effects such as mood disorders or abdominal cramps
- Variable impact on bone density depending on the molecule used
In Western countries, hip fractures cause more deaths among women than some cancers. This highlights the importance of carefully choosing between natural hormonal options or synthetic ones to prevent osteoporosis.
Results of Combined Hormonal Treatments
Results of Combined Treatments
Research shows that the estrogen-progestin combination (EPT) improves vertebral bone mineral density (BMD) by +0.68% per year compared to estrogen alone (95% confidence interval: 0.38 to 0.97%; P = 0.0001). This data highlights the benefits of combined treatments.
The PEPI study also highlighted this superiority by showing a notable increase in DMO among patients receiving combination therapy, compared to those on monotherapy.
| Type of Treatment | Impact on Vertebral Bone Mineral Density | Impact on the Femoral Neck |
|---|---|---|
| Simple hormone therapy | +1.8 % | +0.5% |
| Combined hormone treatment | +2.6 % | +1.5% |
Simple Treatment vs. Combined Treatment
These results confirm significant differences between simple and combined treatments. Combined treatments are part of a comprehensive approach aimed at preserving bone health through appropriate hormonal management.
WHI study data show that both estrogen alone (ET) and estrogen-progestin (EPT) are effective in preventing fractures. However, among non-hysterectomized women, combined therapy provides enhanced bone protection. An increase of 1% in vertebral BMD is associated with an 8% reduction in non-vertebral fractures.
Furthermore, the daily combined progesterone-estrogen treatment has proven to be more effective than estrogen alone in managing postmenopausal osteoporosis. Transdermal forms (patches, gels, or sprays) present a reduced thrombotic risk compared to oral forms, thereby allowing for better personalization based on individual risks.
Recommendations and Treatment Guidelines
The current guidelines emphasize an individualized approach. Menopausal hormone therapy (MHT) can be particularly effective when initiated before the age of 60. These recommendations are based on the clinical evidence previously discussed.
General Recommendations
The choice of treatment depends on several important factors:
| Factor | Influence on the Treatment |
|---|---|
| Age | Ideal Before Age 60 |
| Premature menopause | THM recommended up to 50 years |
| Risk of fracture | Direct the intensity of the treatment |
| Medical history | Guide the selection of treatment |
Comparison of Treatments
In addition to the selection criteria, the data show that THM is effective in reducing the risk of fractures. Here is a comparison of the different therapeutic agents:
| Therapeutic Agent | Reduction of vertebral fractures | Reduction of non-vertebral fractures |
|---|---|---|
| THM | 35 % | 22 % |
| Bisphosphonates | 43 % | 16 % |
| Tibolone | 44 % | 27 % |
Practical Advice
- Consume 1,000 mg of calcium every day
- Conduct regular monitoring of bone mineral density
- Plan an annual re-evaluation with their doctor
Specific Points
Studies highlight micronized progesterone for its better tolerance. Its use in the context of THM should be discussed with a healthcare professional, taking into account the specific risks for each patient.
For women with early menopause, HRT is strongly recommended until about age 50. Regular monitoring of bone density is also essential.
Treatment Monitoring and Adjustments
It is important to monitor bone density, detect any potential side effects, and adjust treatment based on the overall state of health.
In case of treatment discontinuation, a gradual reduction is preferable. If necessary, therapeutic alternatives may be considered to maintain the acquired benefits on bone protection.
Conclusion
By examining clinical data and hormonal mechanisms, the role of progesterone in bone health becomes clear. Research shows that progesterone, in synergy with estradiol, contributes to the maintenance of bone mass and the prevention of osteoporosis after menopause.
Meta-analyses indicate that a combination of progesterone and estradiol further improves bone mineral density compared to estrogen alone. This highlights the interest in a combined therapeutic approach.
Some aspects nevertheless require further investigation:
- The effects of a co-therapy combining progesterone and antiresorptive treatments.
- Changes in bone microarchitecture during treatment.
- The impact on reducing fractures.
"Progesterone deserves to be further studied as an innovative agent to achieve and preserve maximum bone mass, for the prevention of pre- and perimenopausal bone loss, and, in association with antiresorptive therapy, to increase BMD and potentially reduce fractures in postmenopausal women." - Jerilynn C Prior, University of British Columbia
This data reinforces the idea that progesterone, integrated with other treatments, may represent an interesting therapeutic option for managing osteoporosis. Its use requires an individualized approach tailored to the needs of each patient and must be accompanied by careful medical follow-up.
These conclusions also support the natural solutions proposed by Laboratoires üma, offering a complementary perspective in the management of bone health.
About the Laboratoires üma
Laboratoires üma is dedicated to the bone health of women during perimenopause and menopause, offering hormone-free dietary supplements supported by rigorous clinical studies.
Their flagship product, Harmonie Daily, is available for €40.00. It combines essential micronutrients such as calcium and zinc with extracts of seaweed, hops, alfalfa, and red clover. This formula is designed to help maintain strong bones during menopause. Studies conducted in 2021–2022 on over 1,000 women revealed impressive results:
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The Pack Douleurs Articulaires & Osseuses, offered at €60.00, combines formulas that support bone density and promote better mobility. It meets the recommended nutritional needs for women over 50: 1,200 mg of calcium and 800–1,000 IU of vitamin D per day.
All products are developed in France, validated by independent laboratories, and recommended by more than 30,000 doctors and gynecologists. With over 20 years of research in women's health, Laboratoires üma has established itself as a key player in supporting women in maintaining their bone health during menopause.
