9.1 Natural menopause

9.1.1 Cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of death of Australian women with 16.6% and 10% of all deaths in Australian women caused by ischaemic heart disease and stroke respectively  and compares with the 4% of total deaths due to breast cancer(AIHW, 2006 statistics). Distinguishing vascular changes due to menopause versus those due to aging is difficult; however, studies suggest that adverse lipid changes, endothelial dysfunction and pro-hypertensive renal changes are associated with menopause whereas weight gain may be primarily due to aging. The risk of type 2 diabetes mellitus also increases at midlife and the role of oestrogen deficiency remains unclear. The cumulative effect is progression of atherosclerosis and increased prevalence of CVD after menopause. Further complication arises from evidence suggesting that the effect of oestrogen varies according to the underlying vascular pathology; in the presence of established atherosclerosis, as often observed in women > 65 years of age, the athero-protective effect of oestrogen on healthy blood vessels is not observed and pro-inflammatory, prothrombotic and pro-atherogenic changes are apparent.

9.1.2 Osteoporosis

(see Bone Health for Life Website)

Osteoporosis, defined as a condition characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility and susceptibility to fracture, is a significant cause of morbidity and mortality in women (AIHW, 2008). The Dubbo osteoporosis epidemiology study, a longitudinal cohort study, reported an overall fracture incidence of 3250/100000 person-years with a residual lifetime fracture risk of 56% in Australian women aged >60 years.  Osteoporosis is a multi-factorial disease in women with bone loss related to aging, a variety of secondary causes (including drugs and other endocrine disorders) and menopause. The rapid bone loss associated with menopausal oestrogen deficiency is associated with increased bone remodeling/ resorption and a relative deficit in bone formation with greater effect observed in trabecular bone. It has also been postulated that oestrogen deficiency may indirectly contribute to the age related increase in parathyroid hormone implicated in age related bone loss. Acute spinal bone loss (as assessed by dual energy x-ray absorptiometry)  in the first 2 years post-menopause averages 2.5% per year decreasing to 1.8% for years 2-4 and then approximately 1% subsequently. The rate of bone loss in the hip (predominately cortical bone) is approximately half that observed in the spine.

9.1.3 Cognitive decline and dementia

Although cognitive decline and dementia are associated with aging, the contribution of menopausal oestrogen deficiency is unclear. Cross sectional and longitudinal studies indicate that the natural menopause transition is not associated with significant cognitive decline. Observational studies indicate that early hormone replacement therapy (HRT) initiation (at time of menopause) may be protective against dementia. In contrast, the largest randomised controlled trial, Women’s Health Initiative Memory study (WHIMS), reported an increased risk of dementia with late initiation (mean age 71 years) of HRT use. The discrepancies in the data may be related to bias in observational studies and/or timing of HRT initiation. The role of testosterone and effect of different HRT preparations on cognitive function require clarification.

9.2 Premature / Early menopause

Women with premature/ early menopause are at risk from long term complications relating to both the specific cause of menopause (for example, recurrence of breast cancer or complications of Turner’s syndrome) as well as those relating to women with premature menopause generally. Evidence regarding the consequences of premature/ early menopause has been derived from a number of large prospective and cross-sectional observational studies. There are no large randomised controlled trials involving HRT restricted to women with premature menopause that address the long term complications of premature menopause and the relevance of the large scale studies involving HRT and older women (for example, Women’s Health Initiative) to this particular group of women is unclear. There is limited evidence to suggest that risk may vary with the cause of menopause (for example, surgical versus spontaneous) and age at menopause. The risks of long term consequences of premature/ early menopause are summarized in the Table: Long term consequences of premature/early menopause. The pathologic mechanisms have yet to be fully elucidated but oestrogen deficiency is a significant factor as no increased risk in cardiovascular disease, osteoporosis, cognitive dysfunction/ Alzheimer’s and Parkinson’s disease is observed when women are treated with oestrogen therapy to the usual age of menopause (45-50 years). Adverse changes in lipid profile and vascular function secondary to oestrogen deficiency are postulated to result in increased risk of cardiovascular disease. Cross sectional studies indicate that early menopause is associated with 10-25% lower bone mineral density (BMD) compared with age matched controls. This translates to a reduction in BMD by one standard deviation T score by age 65 where menopause occurs at age 40 years. There is limited and conflicting data as to whether the rate of bone loss varies with type of menopause (for example post-oophorectomy, chemotherapy, or spontaneous). Population based studies indicate that women with early menopause have an increased risk of fracture, both vertebral and non-vertebral.

Table: Long term consequences of premature/early menopause

References

• Atsma F, Bartelink ML et al., Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis. Menopause (2006) 13:265-279.
• Gallagher JC. Effect of early menopause on bone mineral density and fractures. Menopause (2007) 14: 567-571.
• Henderson VW and Sherwin BB. Surgical versus natural menopause: cognitive issues. Menopause (2007) 14; 572-579.
• Jones G, Nguyen P et al., Symptomatic fracture Incidence in Elderly men and women: The Dubbo Osteoporosis Epidemiology Study (DOES). Osetoporosis Int (1994) 4:277-282.
• Kalantaridou SN, Naka KK et al., Premature ovarian failure, endothelial dysfunction and estrogen-progestogen replacement. Trends in Endocrinology and Metabolism (2006) 17: 101-109.
• Lobo RA Surgical Menopause and cardiovascular risks. Menopause (2007)14: 562-566.
• Lisabeth LD, Beiser AS et al., Age at natural menopause and risk of ischaemic stroke: The Framingham Heart study. Stroke (2009) 40:1044-1049.
• Mondul AM, Rodriguez C et al., Age at natural menopause and cause-specific mortality. Am J Epidemiol (2005) 162:1089-1097.
• Ossewarde ME, Bots ML et al., Age at menopause, cause specific mortality and total life expectancy. Epidemiology (2005) 16: 556-562.
• Parker WH, Broder MS et al., Ovarian conservation at the time of hysterectomy and long term health outcomes in the Nurse’s Health Study. Obstet Gynecol (2009) 113:1027-1037.
• Rivera CM, Grossardt BR et al., Increased cardiovascular mortality after early bilateral oophorectomy. Menopause (2009) 16:15-23.
• Rocca WA, Grosshardt BR et al., Survival patterns after oophorectomy in premenopausal women: a population based study. Lancet Oncol (2006) 7:821-828.
• Rocca WA, Bower JH et al., Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology (2007) 69: 1074-1083.
• Shuster LT, Rhodes DJ et al., Premature menopause or early menopause: Long term health consequences. Maturitas (2010) 65:161-166.
• Tuppurainen M, Kroger H et al., Risks of perimenopausal fractures- a prospective population based study. Acta Obstet Gynecol Scand (1005) 74: 624-628
• Van der Klift M, deLaet CE, et al., Risk factors for incident vertebral fractures in men and women: the Rotterdam study. J Bone Miner Res (2005) 20: 1172-1180.

10. Management

Content updated December 2010