Reproductive disorders affect the male and female reproductive tracts, impairing fertility, causing pelvic pain and bleeding abnormalities, and increasing the risk of malignancies. The endocrine regulation of reproduction — the hypothalamic-pituitary-gonadal (HPG) axis — is central to understanding these disorders.
Female Reproductive Disorders
Menstrual Disorders
Amenorrhea. Absence of menstruation. Primary amenorrhea: no menarche by age 15. Causes include hypothalamic suppression (low body weight, exercise, stress), pituitary disease (hyperprolactinemia), ovarian failure (Turner syndrome, premature ovarian insufficiency), and outflow tract obstruction (imperforate hymen, Müllerian agenesis). Secondary amenorrhea: absence for 3 months in women with previously normal cycles. Pregnancy must be excluded first.
Abnormal uterine bleeding (AUB). Bleeding that is heavy (menorrhagia), prolonged (>7 days), intermenstrual, or occurs after menopause. The PALM-COEIN classification: structural (Polyp, Adenomyosis, Leiomyoma, Malignancy/hyperplasia) and non-structural (Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic, Not classified). Evaluation includes transvaginal ultrasound, endometrial biopsy (for women >45 or with risk factors), and hysteroscopy.
Dysmenorrhea. Painful menstruation. Primary dysmenorrhea is caused by prostaglandin-mediated uterine contractions, treated with NSAIDs and hormonal contraceptives. Secondary dysmenorrhea results from underlying pathology — most commonly endometriosis or adenomyosis.
Polycystic Ovary Syndrome
PCOS is the most common endocrine disorder in reproductive-age women, affecting 7–15% worldwide. Diagnosis requires 2 of 3 Rotterdam criteria: oligo- or anovulation, clinical or biochemical hyperandrogenism, and polycystic ovaries on ultrasound. Insulin resistance is present in 50–80% of women with PCOS, driving hyperandrogenism and metabolic dysfunction.
Clinical features. Irregular menses, hirsutism, acne, alopecia, and infertility. Long-term risks: type 2 diabetes (5-fold risk), metabolic syndrome, endometrial hyperplasia/cancer (from unopposed estrogen), and cardiovascular disease.
Management. Lifestyle modification (weight loss of 5–10% restores ovulation in 50%) is first-line. Hormonal contraceptives manage hyperandrogenism and regulate menses. Metformin improves ovulation and metabolic outcomes. Clomiphene, letrozole, and gonadotropins are used for ovulation induction. Inositol supplementation may improve metabolic parameters.
Endometriosis
Endometriosis is the presence of endometrial-like tissue outside the uterus — on the peritoneum, ovaries (endometriomas), and deep pelvic structures. It affects 10% of reproductive-age women and is a leading cause of chronic pelvic pain and infertility.
Pathophysiology. Retrograde menstruation (Sampson theory) deposits endometrial cells in the peritoneal cavity. Implantation, growth, and inflammation require estrogen and are promoted by immune dysfunction (impaired clearance of endometrial cells by natural killer cells and macrophages). Deep infiltrating endometriosis causes severe pain by invading nerves and causing fibrosis.
Clinical presentation. Chronic pelvic pain, dysmenorrhea, dyspareunia, dyschezia, and infertility. Symptoms correlate poorly with disease extent.
Diagnosis. Transvaginal ultrasound identifies endometriomas and deep disease. Laparoscopy with histological confirmation is the gold standard. The ASRM classification stages I–IV.
Treatment. Analgesics, hormonal therapy (combined oral contraceptives, progestins, GnRH agonists/antagonists) suppress disease activity but do not cure. Laparoscopic excision of endometriosis lesions improves pain and fertility. For women who have completed childbearing, hysterectomy with bilateral salpingo-oophorectomy is definitive.
Uterine Fibroids (Leiomyomas)
Benign smooth muscle tumors of the uterus, present in 50–80% of women by age 50. Symptoms depend on location: submucosal (heavy bleeding), intramural (pain, pressure), and subserosal (mass effect). Treatment: symptomatic management with NSAIDs, hormonal contraceptives, tranexamic acid, levonorgestrel IUD; myomectomy (for fertility preservation), uterine artery embolization, MRI-guided focused ultrasound, and hysterectomy.
Male Reproductive Disorders
Erectile Dysfunction
The inability to attain or maintain an erection sufficient for satisfactory sexual performance. It affects 40% of men by age 40 and 70% by age 70. Etiology: vascular (atherosclerosis, hypertension, diabetes), neurogenic, hormonal (low testosterone), drug-induced, and psychogenic. Evaluation includes history, physical examination, and morning testosterone measurement.
Treatment. PDE5 inhibitors (sildenafil, tadalafil, vardenafil) are first-line. Intracavernosal injections (alprostadil), vacuum erection devices, and penile prostheses are second-line options. Cardiovascular risk assessment is important, as ED is a sentinel marker for coronary artery disease.
Benign Prostatic Hyperplasia
BPH is a non-malignant enlargement of the prostate gland affecting 50% of men by age 60 and 90% by age 80. It causes lower urinary tract symptoms (LUTS): hesitancy, weak stream, frequency, urgency, nocturia, and incomplete emptying.
Pathophysiology. Androgen-dependent hyperplasia of the transition zone of the prostate compresses the prostatic urethra. Smooth muscle tone in the prostate and bladder neck contributes to obstruction.
Treatment. Alpha-blockers (tamsulosin, alfuzosin) relax prostate smooth muscle. 5-alpha-reductase inhibitors (finasteride, dutasteride) shrink the prostate over months. Combination therapy is more effective than either alone. Minimally invasive therapies (UroLift, Rezūm, TUMT, TUNA) and transurethral resection of the prostate (TURP) are options for refractory disease.
Hypogonadism
Testosterone deficiency affects 2–5% of men. Causes: primary testicular failure (Klinefelter syndrome, chemotherapy, trauma) or secondary hypothalamic-pituitary dysfunction. Symptoms: reduced libido, ED, fatigue, depression, loss of muscle mass, anemia, and osteoporosis. Diagnosis: morning total testosterone <300 ng/dL on two occasions. Testosterone replacement improves symptoms but carries cardiovascular and prostate risks that require discussion.
Infertility
Infertility is defined as failure to achieve pregnancy after 12 months of regular unprotected intercourse. It affects 15% of couples. Male factor contributes to 50% of cases.
Female causes. Ovulatory disorders (PCOS, hypothalamic amenorrhea, premature ovarian insufficiency), tubal disease (infection, endometriosis, previous surgery), uterine factors (fibroids, polyps, synechiae), and age-related decline in oocyte quantity and quality.
Male causes. Sperm production disorders (varicocele, infection, genetic, hormonal), obstructive azoospermia, and ejaculatory dysfunction.
Evaluation. Semen analysis, ovulation assessment (ovulation predictor kits, mid-luteal progesterone), hysterosalpingography (tubal patency), ovarian reserve testing (AMH, antral follicle count), and hormonal evaluation.
Treatment. Ovulation induction (clomiphene, letrozole, gonadotropins), intrauterine insemination (IUI), and in vitro fertilization (IVF). Intracytoplasmic sperm injection (ICSI) for severe male factor. Preimplantation genetic testing (PGT) is available for genetic disorders.
Reproductive Cancers
Cervical cancer. Caused by persistent high-risk HPV (types 16 and 18). Preventable by HPV vaccination and detectable by Pap smear (cytology) and HPV testing at recommended screening intervals. Treatment: conization, hysterectomy, radiation, and chemotherapy.
Ovarian cancer. The most lethal gynecologic cancer. Most present at advanced stage due to non-specific symptoms (bloating, abdominal pain, early satiety). BRCA1/BRCA2 mutations are the strongest risk factor. Treatment: cytoreductive surgery and platinum-based chemotherapy. PARP inhibitors are effective for BRCA-mutated and HRD-positive tumors.
Endometrial cancer. The most common gynecologic cancer. Risk factors: unopposed estrogen (PCOS, obesity, tamoxifen), Lynch syndrome. Presents with postmenopausal bleeding. Diagnosis by endometrial biopsy. Most are endometrioid type with excellent prognosis when detected early. Treatment: hysterectomy with salpingo-oophorectomy, with or without lymph node assessment.
Prostate cancer. See article 03.
Summary
Reproductive disorders encompass hormonal disorders (PCOS, hypogonadism), structural conditions (fibroids, endometriosis, BPH), fertility concerns, and malignancies. PCOS is the most common endocrine disorder in women and requires lifelong management of both reproductive and metabolic health. Endometriosis is a common cause of chronic pelvic pain and infertility. Infertility affects one in six couples, and modern assisted reproductive technologies offer effective solutions. Reproductive cancers — cervical, ovarian, endometrial, and prostate — benefit from screening, early detection, and increasingly targeted therapies.