The endocrinology of the menopause

Changes in the endocrinology of the pituitary-ovarian axis first become manifest at about the age of 40, a selective rise in serum follicle stimulating hormone (FSH) levels occurring at about the same time as a marked acceleration in the loss of primordial follicles from the ovary. FSH levels gradually increase with increasing age in women who continue to cycle regularly. During the menopausal transition, initiated when changes in cycle frequency or in menstrual flow are first observed, both gonadotrophins, oestradiol and inhibin show a marked degree of variability with abrupt changes from typical post-menopausal patterns to those characteristic of the reproductive age group. Within 1-2 years after the final menstrual period or menopause, FSH levels are markedly elevated, luteinizing hormone (LH) levels moderately so, while oestradiol and inhibin levels are low or undetectable. Post-menopausally, adrenal androstenedione is the major source of oestrogen and serum testosterone levels fall moderately, with oophorectomy leading to a further significant fall. Serum sex hormone binding globulin levels fall to a small degree post-menopausally. Areas of persisting controversy include the question of whether oestradiol levels fall with increasing age prior to the onset of the menopausal transition, the relative roles of oestradiol and inhibin in the selective rise of serum FSH and the role of serum androgens post-menopausally.