The hypothalamus–pituitary–ovary axis and type 1 diabetes mellitus: a mini review

A high prevalence of menstrual cycle and fertility disturbances has long been associated with diabetes mellitus. However, rationalization of the intrinsic mechanisms of these alterations is controversial and even contradictory. This review considers (i) the relationship between diabetes mellitus, especially type 1 diabetes mellitus (T1DM), and the hypothalamus–pituitary–ovary (HPO) axis, (ii) the state of our knowledge concerning neuroendocrine control and its relationship with dopaminergic and opioid tonus, and (iii) the influence of the hypothalamus–pituitary–adrenal axis on ovarian function. Functional disturbances that occur as a consequence of diabetes are also discussed, but some T1DM-related diseases of autoimmune origin, such as oophoritis, are not further analysed. Although there are clear indications of a relationship between menstrual and fertility alterations and glycaemic control, in many instances the improvement of the latter is not sufficient to reverse such alterations. It appears that the oligoamenorrhoea and amenorrhoea associated with T1DM is mainly of hypothalamic origin (i.e. failure of the GnRH pulse generator) and may be reversible. The importance of the evaluation of the HPO axis in T1DM women with menstrual irregularities, even in the presence of adequate metabolic control, is emphasized.