5.1 Natural menopause

The average age of spontaneous natural menopause in Western populations is 51 years (range 45-55 years).  The median age of onset of the menopausal transition is 47.5 years (range 41-55 years) with a median duration of 4 years. Observational studies indicate that African, African –American and Hispanic ethnicity and current smoking are factors associated with an earlier age of menopause.

5.2 Spontaneous Early / Premature menopause

The reported prevalence of spontaneous premature menopause (premature ovarian  failure) ranges from 0.9-1.2% women; a lower prevalence is observed in Asian women. Early menopause affects approximately 5% -10% of women. Observational studies have identified a number of risk factors for early / premature menopause including smoking, ethnicity and positive family history (see Early Menopause Website Table: Risk factors associated with spontaneous early/premature menopause). The prevalence of premature ovarian failure in women presenting with secondary amenorrhea has been reported as 4-18%. 

5.3 Medically Induced Early/ Premature Menopause

Approximately 25% of women diagnosed with breast cancer are premenopausal , corresponding to about  1500 Australian women per year under age 45 years.  The incidence of chemotherapy -induced temporary or permanent amenorrhea ranges from 13-100% depending on the age of the woman, type, cumulative dose and duration of chemotherapeutic agent used (increased with alkylating agents such as cyclophosphamide and possibly taxanes)  (see Early Menopause Website Table: Risk factors associated with spontaneous early/premature menopause). Breast cancer chemotherapy has been postulated to advance ovarian age by approximately 10 years. The incidence of spontaneous premature menopause (PM) in a cohort of childhood cancer survivors (including leukaemia, lymphoma, sarcoma, neuroblastoma, renal, bone, and brain tumours; n=2819) ranged from 8% to 30% (compared with 0.8% in control siblings). Increasing age, cumulative dose and number of alkylating agents used, higher dose of ovarian radiation and diagnosis of Hodgkin’s lymphoma were identified as factors with an additive effect on risk observed with multiple factors (see Table: Risk of Premature menopause in child hood cancer survivors).  The incidence of cyclophosphamide –induced premature menopause in women with non- cancer diagnoses such as systemic  lupus erythematosus or Wegener’s granulomatosis varies between 13-83% with increased age at initiation of therapy, cumulative dose and presence of anti-Ro antibodies identified as significant risk factors. Evidence from observational studies indicates that gonadotrophin- releasing hormone(GnRH agonist) co-treatment reduces the gonadotoxic effect of chemotherapy; however, confirmatory data from large randomised controlled trials is needed. 

Table:  Risk of Premature menopause in childhood cancer survivors

Data derived from Sklar CA, Mertans AC et al., 2006.

References:

• LasKari K, Zinzaras E et al., Ovarian function is preserved in women with servere systemic lupus erythematosus after a 6-month course of cyclophosphamide followed by mycophenylate mofetil. Clin Exp Rheumatol (2010) 28:83-6.
• McKinlay SM, Brambilla et al., The normal menopause transition. Maturitas (1992) 14:103-115..
• Nippita TA and Baber RJ. Premature ovarian failure: a review. Climacteric (2007); 10:11-22.
• Sklar CA, Mertens AC et al., Premature menopause in survivors of childhood cancer: A report from the childhood cancer survivor study. J Natl Cancer Inst (2006) 98: 890-896.

6. Early/Premature Menopause

Content updated December 2010