Hyperprolactinemia Hyperprolactinemia can be associated with oligomenorrhea or amenorrhea and should be evaluated with pituitary magnetic resonance imaging (MRI) to exclude macroadenoma or other intracranial pathology (197). Dopamine agonists are first-line agents in otherwise asymptomatic oligoovulatiory or anovulatory patients to restore ovulation (197). Bromocriptine normalizes prolactin levels and induces ovulation in 80% to 90% of patients. It is taken two to three times daily, and most patients will respond to a total dose less than 7.5 mg daily. Side effects can be bothersome and include nausea, vomiting, postural hypotension, and headache. Cabergoline has similarly high efficacy and the advantage of a 0.25 mg twice-weekly dosing schedule and fewer side effects (198).
Hypogonadotropic Hypogonadism Anovulation in the presence of low serum LH, FSH, and estradiol levels defines hypogonadotropic hypogonadism and reﬂects dysfunction within the hypothalamic–pituitary axis. Causes of hypogonadotropic hypogonadism, including craniopharyngiomas, pituitary adenomas, arteriovenous malformations, or other central space-occupying lesions, should be excluded using MRI. Stress, extreme weight loss, anorexia, excessive exercise, and low body mass index are all associated with functional hypothalamic suppression, so good nutrition and optimal body weight should be encouraged to restore ovulation (197,199). Leptin is a hormone produced by peripheral adipocytes that reﬂects energy stores and is deficient in women with diet or exericise-induced amenorrhea (200). Exogenous leptin has been reported to restore ovulation in these women (200,201). Other conditions of hypothalamic dysfunction, such as congenital hypothalamic failure (Kallmann syndrome), can be treated using pulsatile GnRH therapy or gonadotropins. In these patients, both FSH and LH should be administered (197,202). Pulsatile GnRH agonist therapy (25 ng/kg every 60 to 90 minutes) simulates normal physiology and offers some advantages over gonadotropin injections, including fewer multiple gestations and less ovarian hyperstimulation syndrome (OHSS) while maintaining excellent pregnancy rates (202).
Hypothyroidism The prevalence of hypothyroidism among mid-reproductive aged women is 2% to 4% and is mostly a result of autoimmune factors. Menstrual abnormalities, including those from anovulation, are present in 23% to 68% of overtly hypothyroid women and can be corrected with levothyroxine replacement. Subclinical hypothyroidism and the presence of antithyroid antibodies (even if euthyroid) are associated with increased rates of infertility and spontaneous pregnancy loss, although there exists a lack of consensus as to appropriate upper normal limits of TSH and selection bias limits interpretation. In any case, because even very mild or subclinical hypothyroidism can have adverse effects on fetal brain development and subsequent intelligence quotient, it is prudent to screen and treat women with thyroid hormone abnormalities before commencing infertility treatment (203).