8.1 Natural menopause

8.1.1 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 may be associated with menopause whereas weight gain may be primarily due to aging (ESHRE group 2006). The risk of type 2 diabetes mellitus also increases at midlife and the role of oestrogen deficiency remains unclear. Menopause is associated with change in body composition with increased fat mass and decreased lean mass (ESHRE group 2006). Thus the potential cumulative effect is progression of atherosclerosis and increased prevalence of CVD after menopause.

8.1.2 Osteoporosis

(See the Bone Health For Life website for more information)

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 (Begg, Vox et al., 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 (Jones, Nguyen et al. 1994).  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 postmenopause 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.

8.1.3 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 suggest that early hormone replacement therapy (HRT) initiation (at time of menopause) may be protective against dementia (Henderson 2008; Maki and Sundermann 2009). 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.

8.2 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 predominately involving women with non-cancer diagnoses. 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 may be a significant factor as observational studies reported no increased risk in cardiovascular disease, osteoporosis, cognitive dysfunction/Alzheimer’s and Parkinson’s disease when women were 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 (Kalantaridou, Naka et al. 2006). Impaired endothelial function observed in women with premature ovarian failure is reversed with HRT (Kalantaridou, Naka et al. 2004); however, further research is required. 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 are 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 (Tuppurainen, Kroger et al. 1995; Van der Klift, deLaet et al. 2005).
 

Table: Long term consequences of premature/early menopause

8.3 Menopause related to breast cancer

As survival rates for women with breast cancer continue to improve, consideration of the long term consequences of menopause becomes more important. However, the relative contributions of the breast cancer itself, breast cancer therapy, type and age of menopause to the long term risks of cardiovascular disease, cognitive dysfunction and osteoporosis risk is unknown. As women with breast cancer and premature menopause are usually not prescribed oestrogen therapy, they are potentially at risk from the long term sequelae described above in section 8.2. Risk factors for cardiovascular disease, osteoporosis and cognitive dysfunction present in women with breast cancer are summarised in the Table: Risk factors associated with long term sequelae present in women with BC.

Table: Risk factors associated with menopausal long term sequelae observed in women with BC.

See Management of long term consequences of menopause

Selected References:

Shuster LT, Rhodes DJ et al., Premature menopause or early menopause: Long term health consequences. Maturitas (2010) 65:161-166.

9. Management

Content updated May 16, 2011