Volume 4, No. 3, March 2006
Abstract of the Month
Tired of hearing only bad news from the WHI?
Reduction in diabetes incidence with combination hormone replacement
AIMS/HYPOTHESIS: Studies examining the effect of postmenopausal hormone therapy on concentrations of glucose, insulin and diabetes incidence have been inconclusive, in part because many of the studies were too small. We examined the effect of oestrogen plus progestin on diabetes incidence and insulin resistance.
METHODS: The study was a randomised, double-blind trial comparing the effect of daily 0.625 mg conjugated equine oestrogens (CEE) plus 2.5 mg medroxyprogesterone acetate with that of placebo during 5.6 years of follow-up. The participants were 15,641 postmenopausal women enrolled in the Women's Health Initiative Hormone Trial. These women were aged 50 to 79 and all had an intact uterus. Diabetes incidence was ascertained by self-report of treatment with insulin or oral hypoglycaemic medication. Fasting glucose, insulin, and lipoproteins were measured in a random sample at baseline and at 1 and 3 years.
RESULTS: The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2% in the placebo group (hazard ratio 0.79, 95% CI 0.67-0.93, p=0.004). There was little change in the hazard ratio after adjustment for changes in BMI and waist circumference. During the first year of follow-up, changes in fasting glucose and insulin indicated a significant fall in insulin resistance in actively treated women compared to the control subjects (Year 1 to baseline between-group difference -0.22+/-0.10, p=0.03).
INTERPRETATIONS/CONCLUSION: These data suggest that combined therapy with oestrogen and progestin reduces the incidence of diabetes, possibly mediated by a decrease in insulin resistance unrelated to body size. Future studies of alternative postmenopausal hormone therapy regimens and selective oestrogen agonists and/or antagonists should consider the effects of these regimens on insulin resistance and diabetes.
Margolis KL, et al Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial. Diabetologia. 2004 Jul;47(7):1175-87.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db
=pubmed&dopt=Abstract&list_uids=15252707
Comment: Thomas Burke, Anchorage
Does hormone replacement prevent Type II Diabetes?
The question has been raised by several small observational studies with conflicting results*. Now we have 3 large studies that show a significant decrease in diabetes incidence for women taking estrogen with progesterone.
(*A similar small study was published the February gray journal – See Menopause Management)
The Nurses Health Study (N=21,028) was prospective and observational. HERS, the Heart and Estrogen / Progesterone Replacement Study (N=2029) and WHI the Women’s Health Initiative (N=15,641) were both large prospective randomized studies.
All three showed a significant decrease in diabetes incidence of 20% or more. The studies controlled for other risk factors like weight and the WHI showed a decrease in insulin resistance as well. It is highly unlikely that we will see additional studies of this size addressing this issue. Hopefully the diabetes risk data from the estrogen only arm of the WHI will be published soon.
While public attention his focused on other findings of these studies the change in diabetes incidence may be of greater clinical significance. As Type II DM is such a common disease in AI/AN we should include this information in our counseling.
We do not recommend taking hormone replacement for the purpose of disease prevention, even though we know that it is effective at least for osteoporosis, hip fracture and colon cancer. We know that colon cancer is increased to nearly double the prevalence in some AI/AN. Currently it is reasonable to prescribe hormone replacement for the treatment of menopausal symptoms after a discussion of the risks and benefits.
The decreased incidence of Type II DM should now become a routine part of that discussion.
OB/GYN CCC Editorial comment:
Thanks to Dr. Burke for pointing out a possible bias which appears to overlook the benefits of hormone therapy (HT), while emphasizing the negative effects of HT. Another example is presented below. In the estrogen alone trial, estrogen decreased coronary heart disease risk among women 50 to 59 years of age at baseline .
Our goal should be to present balanced non-judgmental counseling to our AI/AN patients.
Lower coronary heart disease risk with CEE: Women 50 to 59 years of age at baseline
CONCLUSIONS: Conjugated equine estrogens provided no overall protection against myocardial infarction or coronary death in generally healthy postmenopausal women during a 7-year period of use. There was a suggestion of lower coronary heart disease risk with CEE among women 50 to 59 years of age at baseline.
Hsia J, et all Conjugated Equine Estrogens and Coronary Heart Disease: The Women's Health Initiative. Arch Intern Med. 2006 Feb 13;166(3):357-65.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db
=pubmed&dopt=Abstract&list_uids=16476878
Effects of conjugated equine estrogen in postmenopausal women with hysterectomy
CONCLUSIONS: The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.
Anderson GL, et al Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004 Apr 14;291(14):1701-12.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db
=pubmed&dopt=Abstract&list_uids=15082697
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OB/GYN
Dr. Neil Murphy is the Obstetrics and Gynecology Chief Clinical Consultant (OB/GYN C.C.C.). Dr. Murphy is very interested in establishing a dialogue and/or networking with anyone involved in women's health or maternal child health, especially as it applies to Native or indigenous peoples around the world. Please don't hesitate to contact him by e-mail or phone at 907-729-3154.
