The function of the hypothalamic-pituitary-ovarian (HPO) axis is influenced by other endocrine glands, including the thyroid, adrenal glands, and pancreas, where functional abnormalities can result in menstrual irregularities or even amenorrhea.
Thyroid
The thyroid secretes thyroxine (T4) and triiodothyronine (T3), which are involved not only in regulating metabolic processes but also in the development and maturation of the gonads, as well as the maintenance of normal menstrual and reproductive functions. Hypothyroidism that occurs before puberty can result in impaired sexual development and delayed onset of puberty, while hypothyroidism during the reproductive years can lead to menstrual irregularities such as oligomenorrhea, hypomenorrhea, or even amenorrhea. Infertility, increased rates of spontaneous miscarriage, preterm delivery, fetal malformations, or neurocognitive deficits are also more common in such cases. Mild hyperthyroidism may lead to increased thyroid hormone secretion and release, resulting in excessive endometrial proliferation and clinical symptoms such as menorrhagia and frequent menstruation, potentially progressing to dysfunctional uterine bleeding. As hyperthyroidism becomes more severe, the processes of secretion, release, and metabolism of thyroid hormones may be inhibited, leading to symptoms such as oligomenorrhea, hypomenorrhea, or amenorrhea.
Adrenal Glands
The adrenal glands synthesize and secrete glucocorticoids and mineralocorticoids, as well as small amounts of androgens and trace amounts of estrogens and progesterone. The adrenal cortex is one of the principal sources of androgens in women. Small amounts of androgens are essential for normal development of pubic and axillary hair, muscle growth, and overall physical development in females. However, excessive androgen secretion can suppress hypothalamic GnRH secretion and antagonize estrogen, leading to ovarian dysfunction, which may result in amenorrhea or even signs of masculinization. In cases of congenital adrenal hyperplasia (CAH), a deficiency in 21-hydroxylase can lead to insufficient synthesis of corticosteroids, triggering compensatory overproduction of adrenocorticotropic hormone (ACTH) and excessive androgen secretion from the adrenal cortex, which may lead to clinical manifestations such as virilization or female pseudohermaphroditism.
Pancreas
Insulin secreted by the pancreatic islets plays an important role not only in glucose metabolism but also in maintaining normal ovarian function. Women with insulin-dependent diabetes mellitus often exhibit ovarian dysfunction. In cases of insulin resistance and hyperinsulinemia, excess insulin can stimulate the overproduction of androgens by the ovary, causing hyperandrogenemia, leading to menstrual disorders or even amenorrhea.