Breast cancer risk associated with different HRT formulations: a register-based case-control study

BACKGROUND: Previous epidemiological studies have inconsistently shown a modestly increased breast cancer risk associated with hormone replacement therapy (HRT). Limited information is available about different formulations – particularly concerning different progestins. METHODS: A case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched breast cancer cases. Conditional logistic regression analysis was applied to estimate crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Stratified analyses were performed to compare the risk of different estrogens, progestins, and combinations. RESULTS: A total of 3593 cases of breast cancer were identified and compared with 9098 controls. The adjusted overall risk estimate for breast cancer (BC) associated with current or past use of HRT was 1.2 (1.1–1.3), and almost identical for lag times from 6 months to 6 years prior to diagnosis. No significant trend of increasing BC risk was found with increasing duration of HRT use, or time since first or last use in aggregate. Many established BC risk factors significantly modified the effect of HRT on BC risk, particularly first-degree family history of BC, higher age, lower education, higher body mass index (BMI), and never having used oral contraceptives (OCs) during lifetime. Whereas the overall risk estimates were stable, the numbers in many of the sub-analyses of HRT formulation groups (estrogens, progestins, and combinations) were too small for strong conclusions. Nevertheless, the BC risk seems not to vary much across HRT formulation subgroups. In particular, no substantial difference in BC risk was observed between HRT containing conjugated equine estrogens (CEE) or medroxyprogesterone acetate (MPA) and other formulations more common in Europe. CONCLUSION: The BC risk of HRT use is rather small. Low risk estimates for BC and a high potential for residual confounding and bias in this observational study do not permit causal conclusions. Apparently, there is not much variation of the BC risk across HRT formulations (estrogens, progestins). However, the small numbers and the overlapping nature of some of the subgroups suggest cautious interpretation

The association of socio-economic position across the life course and age at menopause: the British Women's Heart and Health Study.

OBJECTIVE: To assess the association of indicators of adverse socio-economic position from across the life course with age at menopause. DESIGN: Cross sectional study as part of the British Women's Heart and Health Study. SETTING: 23 British towns. POPULATION: Three thousand and five hundred and thirteen women aged 60-79 years from a total cohort of 4286. Women who underwent a hysterectomy or oophorectomy prior to their 'natural' menopause or who were taking hormone replacement therapy around the perimenopausal period and for whom a biological age at menopause could not be calculated were excluded from this study. MAIN OUTCOME MEASURES: Age at menopause. RESULTS: Most of the 10 indicators of adverse socio-economic position from childhood through to adulthood were linearly associated with a younger age at menopause. In age adjusted analyses, women from manual social classes in childhood began their menopause on average 0.68 years (95% confidence interval [CI] 0.11, 1.3) earlier than those from non-manual social classes. Those who lived in a house as a child without a bathroom began their menopause 0.47 years (95% CI 0.12, 0.82) earlier than those with a bathroom. Those who shared a bedroom began 0.36 years (95% CI 0.03, 0.70) earlier than those who had their own bedroom and finally those who lived in a household with no access to a car as a child began their menopause 0.47 years (95% CI 0.02, 0.95) earlier than those with access to a car. Adult indicators of adverse socio-economic position were similarly associated with earlier age at menopause. Age at completing full time education was not substantively associated with age at menopause. The inverse associations between each of the indicators of both childhood and adult socio-economic position and age at menopause were not importantly affected by adjustment for other reproductive factors but they attenuated by between 6% and 21% with adjustment for adult smoking and body mass index. The inverse associations between each of the childhood indicators of socio-economic position only and age at menopause attenuated markedly (between 12% and 70%) with adjustment for adult leg length. There was a cumulative effect of disadvantage across the life course demonstrated by a strong linear trend between a composite score of the 10 socio-economic indicators and young age at menopause. The age at onset of menopause for women who had 9 or 10 adverse socio-economic indicators was on average 1.70 years (95% CI 0.36, 3.0) younger than that of women with none or only one indicator. CONCLUSIONS: Adverse socio-economic circumstances in childhood, as well as in adulthood, are associated with an earlier age at menopause. The association between childhood deprivation and early menopause may at least in part be mediated via exposures, such as childhood diet, which affect both linear growth and age at menopause