Reproductive Endocrine Disorders

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women, affecting nearly 5%‒10% of women in the age group. Characterized by hyperandrogenism, chronic anovulation leading to oligomenorrhea (or amenorrhea), and metabolic dysfunction, PCOS increases a woman’s risk for infertility, endometrial hyperplasia or carcinoma, and cardiovascular disease. The pathophysiology is incompletely understood but thought to have a multifactorial genetic basis causing altered pulsatile release of gonadotropin-releasing hormone (GnRH), as well as increases in luteinizing hormone (LH), androgens, estrogen, and insulin: The result is chronic anovulation and hirsutism, which define the condition. Diagnosis is one of exclusion; therefore, other causes of abnormal uterine bleeding and hirsutism must be ruled out. Management includes attempting to restore normal ovulation through weight loss, oral contraceptive pills (OCPs), and fertility assistance.

Imaging of the internal female reproductive organs (including the uterus, ovaries, and fallopian tubes) is indicated to diagnose common gynecologic complaints, most commonly in cases of abnormal bleeding, pelvic pain, and to evaluate masses, congenital anomalies, and infertility. Ultrasound is almost always the 1st-line imaging modality of choice, whereas MRI is typically reserved for complicated or indeterminate cases as a follow-up. Computed tomography is almost never used for primary gynecologic assessments. Fallopian tubes are not visible on either ultrasound or MRI if they are normal. The best way to assess tubal patency is by using hysterosalpingography, a fluoroscopic exam in which a dye is injected into the uterine cavity, followed by the study of its flow through the fallopian tubes.

Secondary amenorrhea is defined as the absence of menses for 3 months in a woman with previously regular menstrual cycles or for 6 months in a woman with previously irregular cycles. Etiologies involve either disruptions to the hypothalamic–pituitary–ovarian (HPO) axis or acquired obstructions in the uterus or outflow tract. The most common cause of secondary amenorrhea is pregnancy. The most common pathologic etiologies include functional hypothalamic amenorrhea, polycystic ovary syndrome, hyperprolactinemia, premature ovarian insufficiency, and Asherman's syndrome. The diagnosis is made with a thorough history and physical examination, measurement of hormone levels, a pregnancy test, and imaging with pelvic ultrasonography. A progestin and/or combined estrogen–progestin challenge can help further identify the location of the abnormality. Management depends on the underlying etiology, clinical presentation, and patient desires regarding fertility. Treatment can include lifestyle, medical, and surgical management options.

Hypogonadism is a condition characterized by reduced or no sex hormone production by the testes or ovaries. Hypogonadism can result from primary (hypergonadotropic) or secondary (hypogonadotropic) failure. Hypergonadotropic hypogonadism results when the gonads fail, and hypogonadotropic hypogonadism results from failures in the hypothalamic–pituitary–gonadal axis. Symptoms include infertility, increased risk of osteoporosis, erectile dysfunction, decreased libido, and regression (or absence) of secondary sexual characteristics. Diagnosis is guided by the history, physical exam, measurement of hormone levels, and an evaluation for an underlying etiology. Management is with hormone replacement.

Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Diagnosis of infertility involves laboratory assessments for ovulatory function and a hysterosalpingogram to determine tubal patency in women, and semen analysis to assess the condition in men. Management involves treatment of the underlying pathology when possible, and may include ovulation induction with either timed intercourse or intrauterine insemination (IUI), in vitro fertilization (IVF), and donor gametes, or by gestational surrogates or adoption.

Primary amenorrhea is defined as the absence of menstruation in a girl by age 13 years in the absence of secondary sex characteristics or by the age of 15 years with the presence of secondary sex characteristics. Etiologies can originate in the hypothalamic–pituitary–ovarian (HPO) axis or from anatomic abnormalities in the uterus or vagina. Sometimes other endocrinopathies interfere with the sex hormones enough to suppress menstruation. Important factors to assess when working through the differential diagnosis are whether the patient has breast development (indicating exposure to estrogen from functional ovaries), the presence or absence of a uterus (indicating a potential genetic anomaly), and whether follicle-stimulating hormone (FSH) levels are high, low, or normal (providing insight into the HPO axis). Management includes correcting the underlying hormonal or anatomic issue, providing hormone replacement therapy (HRT), addressing fertility implications, and psychotherapy.

Congenital adrenal hyperplasia (CAH) consists of a group of autosomal recessive disorders that cause a deficiency of an enzyme needed in cortisol, aldosterone, and androgen synthesis. The most common subform of CAH is 21-hydroxylase deficiency, followed by 11β-hydroxylase deficiency. Clinical manifestations depend on the specific enzyme affected. Notably, CAH is the most common cause of ambiguous genitalia in genotypic female individuals. All forms of CAH cause low levels of cortisol, high levels of adrenocorticotropic hormone (ACTH), and adrenal hyperplasia. Laboratory studies help confirm the diagnosis. Lifelong glucocorticoid replacement is needed, and surgical correction of ambiguous genitalia is often performed.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women, affecting nearly 5%‒10% of women in the age group. Characterized by hyperandrogenism, chronic anovulation leading to oligomenorrhea (or amenorrhea), and metabolic dysfunction, PCOS increases a woman’s risk for infertility, endometrial hyperplasia or carcinoma, and cardiovascular disease. The pathophysiology is incompletely understood but thought to have a multifactorial genetic basis causing altered pulsatile release of gonadotropin-releasing hormone (GnRH), as well as increases in luteinizing hormone (LH), androgens, estrogen, and insulin: The result is chronic anovulation and hirsutism, which define the condition. Diagnosis is one of exclusion; therefore, other causes of abnormal uterine bleeding and hirsutism must be ruled out. Management includes attempting to restore normal ovulation through weight loss, oral contraceptive pills (OCPs), and fertility assistance.

Gynecomastia is a benign proliferation of male breast glandular ductal tissue, usually bilateral, caused by increased estrogen activity, decreased testosterone activity, or medications. The condition is common and physiological in neonates, adolescent boys, and elderly men. Some cases are pathological or secondary to chronic liver disease, kidney disease, or hyperthyroidism. The majority of cases are asymptomatic and do not need treatment.