The first menstrual period, menarche, is one of the most significant milestones in a woman’s life. The age at menarche is an important anthropological variable which may influence the overall duration of tissue oestrogen exposure and then affect health in later life. Early menarche is a well established risk factor for the development of breast cancer¹ and endometrial cancer.² Women with a menarcheal age of 10 or 11 years have a 2.2 times greater risk of breast cancer than women who had their first menstrual period at the age of 12 years or more.¹ Those with a menarcheal age of 17 years or more have a 45% lower risk of endometrial cancer.² Early age at menarche is also associated with a risk for obesity³ and depression in later life.⁴ On the other hand, late menarche is associated with lower bone mass and an increased risk of osteoporotic fractures⁵ and Alzheimer’s disease.⁶ Therefore an understanding of potential factors responsible for the age of menarche is of considerable interest and may shed light on our understanding of these diseases.

Age at menarche is a complex trait that is determined by multiple environmental factors, including nutrition, exercise, socioeconomic conditions, psychosocial stimuli, childhood experience, general health,^6,7,8,9,10 and genetic factors. Twin studies have shown that 53–74% of the variation in menarcheal age is attributed to genetic effects.¹¹ Family history is a strong predictor of early menarche,¹⁰ and there are highly significant correlations between menarcheal ages of mothers and daughters.⁷ However, the specific genetic determinants of menarcheal age remain unclear. Oestrogen receptor α (ESR1) plays a distinct physiological role in mediating the specific effects of oestrogen¹²; thus the ESR1 gene may serve as a candidate gene for age …