Dr. Jerilynn C. Prior, Scientific Director, Centre for Menstrual Cycle and Ovulation Research

Ask Jerilynn |

Progesterone Adds to the Positive Bone Effects of Estrogen/Etidronate

Q: 

I saw you on Shaw TV last September and want to say “thanks” for such an informative and helpful presentation. I have been a fan of yours for a number of years, ever since I heard you at a seminar at Royal Columbian, when I was beginning perimenopause. I found your symptoms “diary” most helpful and have shared it with many of my friends over the years.

Being a nurse I always seem to end up checking the pathophysiology of things before I accept them as beneficial to me, and of course menopause was no exception. I heard Dr. John Lee speak about the time I was considering hormone therapy. In 1998 I chose to start on a cream of natural progesterone (50 mg a day). I had to first convince my GP I did not want synthetics if a hormone identical to what I had made for 40 years was available! The reason for hormone therapy was to hopefully ward off osteoporosis because of a strong family history, a congenital abnormality of my back, and BMD showing osteopenia with osteoporosis of one vertebra. I have never looked back. But I did not get a rise in BD as I hoped; after 2 years it stayed much the same. So for the last year I have had estrogen added (as a cream, TriEst 2.5 mg, a natural combination of estrogens).

My bargain with my GP was that if I had no increase after one year I would agree to start a bisphosphonate. My quandary is that at age 58, three years post last period, should I need to go there? I would rather not take Didrocal® because it doesn’t cause a BMD increase, or Fosamax®.

Are there any better, safer alternatives coming along? Is a year long enough to evaluate the benefit of being on a combination of estrogen and progesterone?

A: 

Thank you for your questions. There are now double blind randomized placebo-controlled trial data showing that estrogen with low dose medroxyprogesterone (MPA) prevents hip and other fractures (1). We also now know from controlled trial data that low dose MPA adds significantly to the positive spinal bone changes with estrogen, even if estrogen is in lower than usual doses (2). To be most effective in stimulating osteoblastic new bone formation (3) I believe that the dose of progesterone needs to provide a luteal phase level of progesterone (more than 18 and ideally about 45 nmol/L in the serum).

With any therapy for bone it is important to have at least 1500 mg and ideally 2000 mg of calcium spread out with meals and bedtime from diet plus supplements. In addition you need 800 IU vitamin D/d. It is also important to deal constructively with stress, to be of normal weight and not too skinny (BMI of 23 to 27) and to do regular exercise. (See “ABCs of Midlife Osteoporosis Prevention.”)

I think, from what you've told me, that you have good reasons to be on ovarian hormone therapy for another, approximately, three years. I agree with transdermal estrogen (it may cause a lower risk for thromboembolism than oral estrogen) but you could probably achieve the benefit you need and without premenstrual-like symptoms on half of that dose (1.25 mg/d). I suggest asking your GP to increase your progesterone dose to 150 mg twice a day.

I would ask your GP for a repeat bone density in two years because that is the minimum time needed for an important bone change to be visible. You should go by the results in L1-4 and in the total hip. It will be easier to increase bone density as you get farther from menopause which is a time of natural rapid bone loss.

When you decide to come off estrogen, and if your bone density has not increased to at least a T Score of –1.5, I’d ask your GP for a prescription for etidronate. Start etidronate while still on the estrogen and keeping the full dose progesterone. Only then should you gradually decrease estrogen. I think that the combination of etidronate and full dose progesterone is similar in positive bone effects to the strongest bone medicines we have (such as alendronate or risedronate). And etidronate is much easier to take (the active pill can be taken in the middle of the night), is significantly cheaper and certainly safer than alendronate.

I expect you’ll see a significant positive bone change over the next two years. It is quite likely that the natural estrogen and progesterone you are taking will have equivalent positive effects to the hip fracture prevention shown in the WHI Estrogen plus Progestin arm (1).

Hope this is helpful. All the best to you.

Note: If you have osteoporosis, you should ask your doctor for a prescription for Etidronate as Didrocal®. This works like estrogen to prevent bone loss. Start taking Etidronate before you begin tapering estrogen treatment.

 

Reference List

  1. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in health postmenopausal women: prinicipal results from the Women's Health Initiative Randomized Control trial. JAMA 2002; 288:321-333.
  2. Lindsay R, Gallagher JC, Kleerekoper M, Pickar JH. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA 2002; 287:2668-2676.
  3. Tremollieres FA, Strong DD, Baylink D, Mohan S. Progesterone and promogestone stimulate human bone cell proliferation and insulin-like growth factor 2 production. Acta Endocr 1992; 126:329-337.

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