Insulin-dependent Diabetes Mellitus and Menstrual Dysfunction

Abstract

Disordered reproductive function has long been recognized as a prevalent problem among women of reproductive age who suffer from insulin-dependent diabetes mellitus (IDDM). Delay in menarchial age is frequently seen if IDDM develops in the peripubertal years and some form of menstrual dysfunction is found in nearly one-third of all women of reproductive age with IDDM. This review summarizes some of the prevailing views regarding the mechanisms through which uncontrolled IDDM is thought to disrupt normal hypothalamic-pituitary-gonadal function. Although animal studies have suggested that poorly controlled IDDM may adversely affect the uterovaginal outflow tract and/or ovarian function, no clinical studies have suggested that abnormal uterine or ovarian function underlies the menstrual dysfunction observed in young diabetic women. Similarly, pituitary function as assessed by basal gonadotrophins and gonadotrophin-releasing hormone (GnRH)-stimulated gonadotrophin release appears to be normal in young women with IDDM. Moreover, although there has been some suggestion that pituitary function may decline with increasing duration of diabetes, this issue has not been thoroughly investigated. It appears that the oligo/amenorrhea noted in IDDM is principally hypothalamic in origin and may represent intermittent (and perhaps reversible) failure of the GnRH pulse generator, similar to the situation observed in women who engage in endurance training or who suffer from anorexia nervosa. Although the exact pathophysiological mechanisms that subserve dysfunction of the GnRH neuronal system are not well understood, attention has focused on increased central opioidergic activity, increased central dopaminergic activity, and central glucose deprivation. In this era of emphasis on tight glycaemic control and its impact in preventing diabetes complications, the consequences of IDDM on reproductive potential appear to be important and must be included in future investigative efforts.

Menopause in Type 1 Diabetic Women

“…Because insulin and androgen levels are highly correlated in women with PCOS, one may speculate that the young age at menopause in women with type 1 diabetes may be mediated, in part, through peripheral hyperinsulinemia and/or hyperandrogenemia. However, the occurrence of PCOS in women with type 1 diabetes has rarely been reported (1). Thus, factors unrelated to long-term diabetes may also be important determinants of the menopause transition.…”

“…oung women with type 1 diabetes have a delayed age at menarche and are at higher risk for having menstrual irregularities than nondiabetic women of similar age (1)(2)(3). Of the women with type 1 diabetes, Ͼ30% report problems, such as amenorrhea, polymenorrhea, and oligomenorrhea throughout their reproductive years.…”

Leptin accelerates the onset of puberty in normal female mice.

“…puberty, cyclicity, pregnancy, and lactation (6), and is a critical determinant of population growth (24,25). In humans, states of negative energy balance (e.g., starvation) uncontrolled diabetes, and high intensity exercise are associated with disruption of cyclicity (26)(27)(28). Fecundity is better correlated with body weight and adiposity than with age (6), and the trend towards puberty occurring at younger ages in developed countries during this century may be determined by improved nutrition and adiposity in children (8).…”

Central Injection of Ketone Body Suppresses Luteinizing Hormone Release via the Catecholaminergic Pathway in Female Rats

“…For instance, glucoprivation causes enhanced fatty acid oxidation and ketosis [13]. Diabetes mellitus is a ketotic condition, and women with type 1 diabetes often show various reproductive problems [14,15]. Dairy cows during early postpartum periods show a low LH pulse frequency concomitantly with an increase in 3-hydroxybutyrate (3HB), a ketone body, concentrations [16].…”