Mechanisms of nulliparity that can mediate the risks associated with infertility include:
Anovulatory menstrual cycles
Higher serum levels of estrogen may lead to infrequent or anovulation which consequently reduces progesterone protection of the endometrium (uterine lining) from high levels of unopposed endogenous (natural) estrogen. An absence of childbearing results in a prolonged exposure of estrogen without sufficient progesterone (the hormone of pregnancy). In anovulation, ovaries do not release an egg and the ovulation does not take place.
Elevated levels of androstenedione
Androstenedione is a precursor of testosterone and other androgens (male sex hormones), as well as of estrogens like estrone, in the body. Androstenedione is converted into estrogens, reduces the clearance (volume of plasma from which a substance is completely removed per unit time) of estrogen from the blood. This results in continuous exposure of the endometrium to high levels of estrogen. Elevated androstenedione levels can cause symptoms or signs of hyperandrogenism (elevated levels of androgens) in women.
The most common conditions associated with hyperandrogenism are polycystic ovary syndrome or PCOS, a set of symptoms caused by androgen excess in females, and various cancers that can cause androgen excess. In females, the conditions usually present are some combination of acne, seborrhea (inflamed skin), hair loss on the scalp, increased body and/or facial hair (hirsutism), and an elevated sex drive or libido.
The lack of monthly sloughing of the lining of the endometrium
The lack of monthly sloughing of the lining of the endometrium could result in the excessive proliferation of the cells of the residual endometrial tissue (endometrial hyperplasia).
Most cases of endometrial hyperplasia result from high levels of estrogens, combined with insufficient levels of the progesterone-like hormones which ordinarily counteract estrogen's proliferative effects on this tissue.
Gynecologic cancers include vulva, vaginal, cervical, endometrial, and ovarian/tubal/peritoneal cancers, the latter of which are still classified as one disease. These patients face difficulty conceiving secondary to obesity, polycystic ovarian syndrome and chronic anovulation. Secondary to these issues it is recommended an initial consultation with a reproductive endocrinologist in order to assess the patient’s reproductive options and likelihood of conception. This ensures appropriately informed expectations regarding reproductive potential and thus the patient’s desire to proceed with fertility-preserving therapy.