This international expert executive summary confirms that much lower dose HRT (estrogen plus appropriate androgen) (as by the parenteral route) is as beneficial as the conventional oral dose, with far less risks for adverse (fluid retention & liver, breast & thrombosis) effects, and if started early, giving longterm protection against memory loss, fractures and death from vascular disease and breast cancer. The evidence contradicts common misperceptions and myths:
March 29–30, 2008 Summary of the First INTERNATIONAL MENOPAUSE SOCIETY
IMS Global Summit on menopause-related issues: HRT in the early menopause:
A Pines, D. Sturdee, M. Birkhäuser, F. Naftolin, R. Farmer, et al. on behalf of the IMS see link
Hormone replacement therapy (HRT) remains the first-line and most effective treatment for menopausal symptoms.
. Level A evidence refers to data from randomized controlled trials, whereas Level B evidence comes from case–control/observational studies. As pointed out in the Summit’s title, the focus of discussions was the effects of HRT first administered during the early postmenopausal period.
1. QUALITY OF LIFE AND MENOPAUSE
· In symptomatic postmenopausal women, quality of life and sexuality are improved by HRT and, in the presence of
symptoms of androgen deficiency, by additional androgen administration.
· In some cultures/ for some women, vaginal bleedings are unacceptable; if bleeding cannot be eliminated, alternatives may be used.
· There is no evidence that so-called ‘natural’ products and unregulated hormone products (compounded bio-identical) significantly improve quality of life.
2. LONGTERM BENEFITS OF HRT POST MENOPAUSE
HRT, coronary heart disease, stroke and thromboembolism
· HRT in women 50–59 years does not increase CHD risk in health and may even decrease risk in this age group[A]
· Estrogen-alone therapy in the age group 50–59 was associated with significantly less coronary calcification (equivalent to a smaller plaque burden), which is consistent with findings of a lower coronary intervention score in women of this age in the WHI study10. [A]
· Early harm (more coronary events during the first 2 years of HRT) was not observed in the early postmenopausal period. The number of CHD events decreased with duration of HRT in both WHI clinical trials[A]
· Data derived from randomized controlled trials in the age group 50–59 are similar to the older observational data suggesting a protective effect of HRT on coronary disease9. [A, B]
· It is unclear at present whether there is a statistical increase in ischemic stoke with standard HRT in healthy women aged 50–59. The WHI data showed no statistically significant increase in risk; nevertheless, even if statistically increased, as found in the Nurses’ Health Study, the low prevalence of this occurrence in this age group makes the attributable risk extremely small. [A,B]
· The risk of venous thrombosis is approximately two-fold higher with standard doses of oral HRT, but is a rare event in that the background prevalence is extremely low in a healthy woman under 60 years of age. [A]
· The risk of venous thrombosis is possibly less with transdermal, compared with oral estrogen therapy [B]
· There is a wide variation across the world in the incidence of breast cancer and its risk factors.
· There are multiple risk factors for breast cancer, including life-style factors especially alcohol intake, obesity and lack of exercise. These need to be included during counseling to put the magnitude of risk of HRT into perspective [B]
· After 5 years’ use of combined estrogen and progestogen, there is a small increase in risk of breast cancer in North American women of about eight extra cases per 10,000 women per year. However, no significant increase was seen in women without prior use of HRT in the WHI study. [A]
· Estrogen-only use does not cause an increase in breast cancer for up to 7 years21. [A] In observational studies, a small increase in the risk with estrogen-alone therapy appears with long-term use22. [B]
· Women using combined HRT before a diagnosis of breast cancer have a reduced mortality23. [B]
· A decline in the incidence of breast cancer in the USA started before the WHI publication and can be partially related to fluctuation in screening. There has been no decline in breast cancer registration in the UK following the Million Women Study report, nor in Norway, Canada, the Netherlands and countries with stable screening programmes25. [B]
· Combined estrogen and progestogen therapy may cause increased breast density in up to 50% of postmenopausal women, dependent on the regimen (dosage, type of progestogen). The effect of estrogen alone is smaller26. [A]
· The effect on breast density is dose-related. Ultra-low-dose regimes do not cause perceptible change in density[A]
· The average increase in breast density under standard-dose HRT is only about 5–10%28. [A]
· Increased baseline breast density is a risk factor for breast cancer29. There are no data to support a direct association between HRT-induced breast density changes and the risk of developing breast cancer.
· Many women who develop breast cancer have no known risk factors other than growing older. most women with known risk factors do not develop breast cancer.
· Individual risk analysis for breast cancer is strongly recommended in clinical practice30.
*Overall HRT is effective in preventing all osteoporosis-related fractures even in patients at low risk of fracture[A]
*Although no head-to-head studies have compared HRT to bisphosphonates in terms of fracture reduction, there is
no evidence to suggest that bisphosphonates or any other antiresorptive therapy are superior to HRT.
* It is therefore suggested that, in 50–59-year-old postmenopausal women, HRT is a cost-effective first-line
treatment in the prevention of osteoporotic fractures.
* Even below standard-dose preparations maintain positive influence on bone indices such as BMD[A]
· HRT has a positive effect on osteoarthritis and the integrity of intervertebral disks.
*At present, there is no evidence of substantial cognitive decline across the menopausal transition[A] However, many women experience cognitive difficulties in association with vasomotor symptoms, sleep disturbances & mood changes.
*Verbal memory performance relates with the objective number of hot flushes women experience but not to the number of hot flushes they report.
*Clinical trials find no cognitive benefit among women initiating HRT late postmenopause (i.e. after age 65).
*Observational studies show a decreased risk of Alzheimer’s disease in hormone users and typically involve women who initiated estrogen therapy early in the menopausal transition. [B]
*Limited data exist on the effect of progestogen added to estrogen in the early postmenopause period. Clinical trial data suggest no cognitive benefit with MPA early in the menopause. [A]