Medical School · Year 3 · Obgyn · includes a quiz and discussion video

Seminar 11: Menstrual Disorders

OB/GYN Clerkship

Learning Objectives

By the end of this seminar, students will be able to:

1. Describe the phases, hormonal regulation, and endometrial changes of the normal menstrual cycle
2. Evaluate abnormal uterine bleeding using the FIGO terminology and PALM-COEIN classification system
3. Differentiate structural from non-structural causes of abnormal uterine bleeding and select appropriate diagnostic studies
4. Diagnose and evaluate primary and secondary amenorrhea using systematic anatomic and hormonal frameworks
5. Distinguish primary from secondary dysmenorrhea and apply evidence-based treatment algorithms
6. Recognize premenstrual syndrome and premenstrual dysphoric disorder and initiate first-line pharmacologic therapy

Seminar Outline

Section 1: Normal Menstrual Cycle

The menstrual cycle is a coordinated sequence of hormonal and physiologic events that prepares the reproductive tract for potential pregnancy each month. The cycle begins with the menstrual phase spanning approximately days 1 through 5, during which the endometrium sheds in the absence of implantation. The follicular phase encompasses days 1 through 14 and is characterized by progressive follicular development under the influence of rising estrogen levels. Ovulation occurs around day 14, triggered by a surge in luteinizing hormone, and the luteal phase spans days 15 through 28 as the corpus luteum produces progesterone to support a potential pregnancy before involuting if conception does not occur.

Hormonal regulation of the menstrual cycle involves a precisely orchestrated interplay among the hypothalamus, pituitary gland, and ovaries. Gonadotropin-releasing hormone is secreted in a pulsatile fashion from the hypothalamus and stimulates the anterior pituitary to release follicle-stimulating hormone and luteinizing hormone. Follicle-stimulating hormone drives follicular recruitment and development, while the luteinizing hormone surge triggers ovulation. Estrogen, produced primarily by the developing follicle, drives endometrial proliferation, and progesterone, secreted by the corpus luteum, transforms the endometrium into a secretory state capable of supporting implantation.

Normal menstrual parameters provide the clinical framework for identifying deviations that may require investigation. Menarche typically occurs between ages 10 and 16, with the median age approximately 12.5 years. A normal menstrual cycle length ranges from 24 to 38 days, with menstrual flow lasting 4 to 8 days and total blood loss between 20 and 80 milliliters. Cycle regularity is defined as variation of no more than 7 to 9 days between the shortest and longest cycles, and deviations from any of these parameters may warrant evaluation depending on the patient's age, reproductive status, and associated symptoms.

The endometrium undergoes characteristic histologic changes during each phase of the menstrual cycle that correlate with the prevailing hormonal milieu. During the proliferative phase, rising estrogen levels stimulate glandular elongation and stromal proliferation, resulting in progressive thickening of the endometrium. Following ovulation, progesterone from the corpus luteum induces the secretory phase, characterized by glandular secretion of glycogen-rich fluid and stromal edema with decidualization. In the absence of implantation, declining progesterone levels trigger prostaglandin release, vasoconstriction of spiral arterioles, tissue ischemia, and ultimately menstrual shedding with breakdown and expulsion of the functional layer of the endometrium.

<image>Panel A: Schematic diagram of the menstrual cycle phases showing the menstrual phase (days 1 to 5), follicular phase (days 1 to 14), ovulation (day 14), and luteal phase (days 15 to 28) with corresponding ovarian events. Panel B: Hormonal axis illustration depicting hypothalamic GnRH pulsatility, pituitary FSH and LH secretion patterns, and ovarian estrogen and progesterone production across the cycle. Panel C: Graphical plot of serum hormone levels throughout the cycle showing the estrogen peak preceding the LH surge at midcycle and the progesterone plateau during the luteal phase. Panel D: Endometrial histology comparison showing proliferative phase with elongated glands and mitotic activity, secretory phase with coiled glands and stromal edema, and menstrual phase with tissue breakdown and hemorrhage.</image>

Section 2: Abnormal Uterine Bleeding

Abnormal uterine bleeding is defined and categorized using standardized FIGO terminology to ensure consistent clinical communication. Heavy menstrual bleeding refers to excessive menstrual blood loss exceeding 80 milliliters or heavy flow as reported by the patient, while intermenstrual bleeding describes bleeding that occurs between expected menstrual periods. Frequent menstrual bleeding is defined as cycles shorter than 24 days, and infrequent menstrual bleeding describes cycles longer than 38 days. Irregular menstrual bleeding refers to cycle-to-cycle variation exceeding 20 days, and prolonged menstrual bleeding is defined as flow lasting longer than 8 days.

The PALM-COEIN classification system provides a structured framework for identifying and categorizing the causes of abnormal uterine bleeding. The structural causes, represented by the acronym PALM, include polyps, adenomyosis, leiomyomas, and malignancy or hyperplasia. The non-structural causes, represented by COEIN, include coagulopathy, ovulatory dysfunction, endometrial causes, iatrogenic factors, and causes not otherwise classified. This system allows clinicians to systematically consider both structural and functional etiologies, recognizing that multiple causes may coexist in a single patient and contribute to bleeding symptoms.

The evaluation of abnormal uterine bleeding follows a stepwise approach beginning with exclusion of pregnancy and assessment for systemic causes. A pregnancy test is the essential first step regardless of the patient's stated contraceptive use. A complete blood count assesses for anemia, while thyroid-stimulating hormone and prolactin levels screen for common endocrine causes of ovulatory dysfunction. Coagulation studies are indicated when heavy bleeding has been present since menarche, suggesting an underlying bleeding disorder. Pelvic ultrasound evaluates for structural causes, and endometrial biopsy is performed in women older than 45 or those with risk factors for endometrial hyperplasia or cancer.

Endometrial biopsy is a critical component of the workup for abnormal uterine bleeding in specific clinical scenarios. Women older than 45 presenting with any pattern of abnormal uterine bleeding require tissue sampling to exclude malignancy. Persistent bleeding that has failed to respond to medical treatment warrants biopsy regardless of age, as does the presence of risk factors for endometrial cancer including obesity, polycystic ovary syndrome, or chronic anovulation. All postmenopausal bleeding mandates evaluation, and a transvaginal ultrasound demonstrating endometrial thickness greater than 4 millimeters in a postmenopausal woman is an indication for tissue sampling. The biopsy is typically performed in the office using a disposable endometrial sampling device.

<image>Panel A: FIGO terminology diagram defining heavy menstrual bleeding, intermenstrual bleeding, frequent bleeding, infrequent bleeding, irregular bleeding, and prolonged bleeding with their numerical thresholds. Panel B: PALM-COEIN classification system displayed as a two-column framework with structural causes (polyp, adenomyosis, leiomyoma, malignancy) and non-structural causes (coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, not classified). Panel C: Stepwise evaluation algorithm showing pregnancy test followed by CBC, TSH, prolactin, coagulation studies, ultrasound, and endometrial biopsy with indications for each. Panel D: Endometrial biopsy technique illustration showing transcervical sampling device with indications including age over 45, persistent AUB, risk factors, and postmenopausal bleeding.</image>

Section 3: Structural Causes of AUB

Endometrial polyps are localized overgrowths of endometrial tissue that project into the uterine cavity and are a common cause of intermenstrual or heavy menstrual bleeding. These polyps are composed of endometrial glands, stroma, and blood vessels and may be sessile or pedunculated. Diagnosis is made by transvaginal ultrasound, which may show focal endometrial thickening, saline infusion sonography that provides superior visualization of intracavitary lesions, or hysteroscopy which allows direct visualization and concurrent removal. While the vast majority of polyps are benign, there is a small risk of malignancy estimated at 1 to 3 percent that increases with patient age, and hysteroscopic polypectomy is the standard treatment.

Adenomyosis is a condition in which endometrial glands and stroma are found within the myometrium, causing uterine enlargement and characteristic symptoms. Patients typically present with progressively worsening dysmenorrhea and heavy menstrual bleeding, and physical examination often reveals a diffusely enlarged, globular, and tender uterus. Transvaginal ultrasound demonstrates a heterogeneous myometrium with characteristic "venetian blind" shadowing, while MRI shows thickening of the junctional zone exceeding 12 millimeters. Medical management includes hormonal therapy with oral contraceptive pills, the levonorgestrel intrauterine device, or gonadotropin-releasing hormone agonists, while hysterectomy provides definitive treatment for women who have completed childbearing.

Uterine leiomyomas, commonly known as fibroids, are the most prevalent pelvic tumors in women and are classified by their location relative to the uterine wall. Submucosal fibroids distort the endometrial cavity and are most strongly associated with heavy menstrual bleeding, while intramural fibroids lie within the myometrium and may affect both bleeding and fertility depending on their size and proximity to the cavity. Subserosal fibroids project from the outer surface of the uterus and typically cause bulk symptoms rather than bleeding. Medical management includes hormonal therapy, tranexamic acid, and gonadotropin-releasing hormone agonists, while procedural options range from uterine artery embolization and myomectomy to hysterectomy depending on symptom severity and reproductive goals.

Endometrial malignancy and hyperplasia represent the most serious structural causes of abnormal uterine bleeding and must be excluded in at-risk patients. Endometrial hyperplasia without atypia carries a malignancy risk of 1 to 3 percent and is managed with progestin therapy, while atypical hyperplasia carries a risk of concurrent or progressive cancer of 25 to 40 percent and typically warrants hysterectomy. Endometrial cancer is the most common gynecologic malignancy in the developed world and most commonly presents with postmenopausal bleeding, though it may also cause irregular or heavy bleeding in premenopausal women. Staging and treatment are based on the surgical findings and histologic features, with the prognosis depending on the type, grade, and extent of disease.

<image>Panel A: Endometrial polyp visualization showing transvaginal ultrasound with focal thickening, saline infusion sonography outlining the intracavitary lesion, and hysteroscopic view of a pedunculated polyp. Panel B: Adenomyosis imaging comparison showing ultrasound with venetian blind shadowing in heterogeneous myometrium and MRI demonstrating junctional zone thickening greater than 12 millimeters. Panel C: Fibroid classification diagram illustrating submucosal (types 0 to 2), intramural (types 3 to 4), and subserosal (types 5 to 7) locations with their respective symptom profiles. Panel D: Endometrial hyperplasia and cancer progression pathway from normal endometrium through hyperplasia without atypia to atypical hyperplasia to endometrial carcinoma with associated malignancy risk percentages.</image>

Section 4: Non-Structural Causes of AUB

Coagulopathy is an important but often underdiagnosed cause of heavy menstrual bleeding, particularly in adolescents and young women. Von Willebrand disease is the most common inherited bleeding disorder and should be suspected when heavy menstrual bleeding has been present since menarche, especially with a family history of bleeding. Platelet disorders including immune thrombocytopenic purpura and other acquired or congenital conditions may also present with menorrhagia. Clinical clues suggesting coagulopathy include heavy bleeding from menarche, easy bruising, bleeding after dental procedures, and a family history of bleeding disorders. The workup includes von Willebrand factor antigen, ristocetin cofactor activity, factor VIII levels, and platelet function testing.

Ovulatory dysfunction is the most common non-structural cause of abnormal uterine bleeding and is characterized by irregular or absent ovulation leading to unpredictable bleeding patterns. Polycystic ovary syndrome is the most prevalent cause of ovulatory dysfunction in reproductive-age women, producing irregular cycles due to chronic anovulation and hyperandrogenism. Hypothalamic amenorrhea results from physiologic stress, excessive exercise, or low body weight, all of which suppress the hypothalamic-pituitary-ovarian axis. Thyroid disease, both hypothyroidism and hyperthyroidism, and hyperprolactinemia from pituitary adenoma or medications can disrupt normal ovulatory function. Perimenopause represents a physiologic transition characterized by increasingly irregular cycles due to declining ovarian function and erratic hormonal fluctuations.

Endometrial causes of abnormal uterine bleeding include chronic endometritis, a condition diagnosed by the presence of plasma cells on endometrial biopsy. Chronic endometritis is associated with common endometrial pathogens and may present with intermenstrual bleeding, pelvic pain, or infertility. The condition is often underrecognized because symptoms may be subtle and overlap with other causes of abnormal bleeding. Treatment with a course of antibiotics, typically doxycycline, leads to resolution of both the histologic findings and the associated bleeding in the majority of patients, and repeat biopsy may be performed to confirm cure in cases of persistent symptoms or infertility.

Iatrogenic causes of abnormal uterine bleeding are common and should be systematically considered in any patient presenting with unscheduled or heavy bleeding. The copper intrauterine device is well known to increase menstrual blood loss and cramping, which is the most common reason for discontinuation. Hormonal contraceptives of all types may cause breakthrough bleeding, particularly during the first several months of use, and patient counseling about this expected side effect improves continuation rates. Anticoagulant medications including warfarin, heparin, and direct oral anticoagulants can significantly increase menstrual blood loss. Additional iatrogenic causes include selective serotonin reuptake inhibitors, which affect platelet function, and tamoxifen, which has estrogenic effects on the endometrium.

<image>Panel A: Von Willebrand disease screening algorithm showing clinical clues of heavy bleeding from menarche, easy bruising, and family history leading to laboratory testing including vWF antigen, ristocetin cofactor, and factor VIII. Panel B: Ovulatory dysfunction etiology diagram showing PCOS (most common), hypothalamic causes (stress, exercise, weight), thyroid disease, hyperprolactinemia, and perimenopause with their respective hormonal patterns. Panel C: Chronic endometritis histologic image showing plasma cell infiltration of endometrial stroma with associated clinical features and doxycycline treatment protocol. Panel D: Iatrogenic bleeding causes illustrated showing copper IUD with increased blood loss, hormonal contraceptive breakthrough bleeding timeline, and anticoagulant-associated menorrhagia management.</image>

Section 5: Management of AUB

Medical management of abnormal uterine bleeding offers multiple pharmacologic options that can be tailored to the underlying cause and patient preferences. Nonsteroidal anti-inflammatory drugs reduce menstrual blood loss by 20 to 50 percent through inhibition of prostaglandin synthesis and are effective for both heavy bleeding and associated dysmenorrhea. Tranexamic acid, an antifibrinolytic agent, reduces bleeding by approximately 50 percent and is taken only during the days of menstrual flow. Combined oral contraceptive pills regulate the menstrual cycle and reduce bleeding by stabilizing the endometrium, while progestins can be administered cyclically or continuously depending on the clinical scenario. The hormonal intrauterine device is among the most effective medical treatments for heavy menstrual bleeding, producing a dramatic reduction in blood loss and often amenorrhea, and gonadotropin-releasing hormone agonists provide short-term suppression but are limited by hypoestrogenic side effects.

Surgical options for abnormal uterine bleeding are considered when medical management fails or when structural pathology requires procedural intervention. Hysteroscopic polypectomy addresses endometrial polyps, while myomectomy removes fibroids and preserves the uterus for women desiring future fertility. Endometrial ablation destroys the endometrial lining using various energy modalities and is highly effective for heavy menstrual bleeding in women who have completed childbearing, though it is not a sterilization procedure and contraception must be continued. Hysterectomy provides definitive treatment and is appropriate when other options have failed or are contraindicated. Uterine artery embolization is a minimally invasive radiologic procedure that reduces fibroid blood supply and is effective for bleeding and bulk symptoms while preserving the uterus.

Emergency management of acute abnormal uterine bleeding requires rapid assessment and intervention to stabilize the patient. Intravenous conjugated estrogen is administered for acute hemorrhage to promote rapid endometrial stabilization and hemostasis. High-dose combined oral contraceptive pills may be used in a tapered regimen to control acute bleeding in hemodynamically stable patients. Dilation and curettage is performed when pharmacologic measures fail to control bleeding or when tissue diagnosis is urgently needed. Blood transfusion is indicated for patients with severe anemia and hemodynamic compromise. In refractory cases, intrauterine balloon tamponade using a Foley catheter may serve as a temporizing measure while definitive treatment is planned.

Follow-up care after initiation of treatment for abnormal uterine bleeding ensures adequate response and identifies the need for treatment modification. Response assessment includes evaluation of symptom improvement, return to normal bleeding patterns, and patient satisfaction with the chosen therapy. Hemoglobin monitoring is important to document resolution of anemia, and iron supplementation should be continued until iron stores are replete even after bleeding has normalized. Recurrence of symptoms may necessitate a change in medical therapy, consideration of procedural or surgical options, or re-evaluation for alternative diagnoses. Patients on long-term medical management require periodic reassessment to ensure ongoing efficacy and tolerability of the selected regimen.

<image>Panel A: Medical management algorithm for AUB showing first-line options (NSAIDs, tranexamic acid, combined OCP) and second-line options (hormonal IUD, progestins, GnRH agonists) with their respective efficacy percentages. Panel B: Surgical options comparison showing hysteroscopic polypectomy, myomectomy approaches, endometrial ablation techniques, and hysterectomy routes with indications for each. Panel C: Emergency management protocol for acute uterine hemorrhage showing stepwise approach from IV estrogen and high-dose OCP through D&C and transfusion to intrauterine balloon tamponade. Panel D: Follow-up monitoring framework showing hemoglobin tracking, symptom assessment, iron supplementation protocol, and decision points for treatment escalation or modification.</image>

Section 6: Primary Amenorrhea

Primary amenorrhea is defined as the absence of menarche by age 15 in the presence of normal secondary sexual characteristics, by age 13 in the absence of any breast development, or three years after the onset of breast development without the onset of menses. These age-based definitions account for the normal variation in pubertal development while identifying patients who fall outside expected timelines. The clinical significance of primary amenorrhea lies in its association with a range of congenital and acquired conditions that may affect reproductive, endocrine, and psychological health. Early identification and evaluation allow timely intervention and appropriate counseling for affected patients and their families.

The evaluation of primary amenorrhea follows a systematic approach beginning with assessment of pubertal development and reproductive anatomy. Physical examination focuses on the presence and stage of breast development and pubic hair using Tanner staging, as well as vaginal patency and the presence of a uterus. Initial laboratory studies include follicle-stimulating hormone, luteinizing hormone, prolactin, and thyroid-stimulating hormone to assess the hypothalamic-pituitary-ovarian axis. Pelvic ultrasound evaluates for the presence and morphology of the uterus and ovaries, and karyotype analysis is indicated when gonadotropin levels are abnormal to identify chromosomal causes such as gonadal dysgenesis.

The causes of primary amenorrhea are organized by anatomic level to facilitate a logical diagnostic approach. Outflow tract abnormalities include imperforate hymen, which presents with cyclical pain and hematocolpos, transverse vaginal septum, and Mullerian agenesis in which the uterus and upper vagina are congenitally absent despite normal ovarian function. Ovarian causes include gonadal dysgenesis, most commonly Turner syndrome, and premature ovarian insufficiency. Pituitary causes include prolactinoma and other tumors that disrupt gonadotropin secretion. Hypothalamic causes include functional hypogonadotropic hypogonadism from stress, low body weight, or excessive exercise, as well as congenital gonadotropin-releasing hormone deficiency.

Several specific conditions merit individual attention due to their clinical importance in the differential diagnosis of primary amenorrhea. Turner syndrome, characterized by a 45,X karyotype, presents with short stature, webbed neck, shield chest, and streak gonads that fail to produce estrogen and require hormone replacement therapy. Mullerian agenesis, also known as Mayer-Rokitansky-Kuster-Hauser syndrome, presents with absent uterus and upper vagina but normal ovarian function and a 46,XX karyotype. Complete androgen insensitivity syndrome occurs in 46,XY individuals who develop a female phenotype due to nonfunctional androgen receptors and present with absent uterus, absent pubic hair, and blind-ending vagina. Constitutional delay of puberty is a diagnosis of exclusion characterized by a family history of late development and eventual spontaneous onset of menses.

<image>Panel A: Diagnostic criteria for primary amenorrhea showing the three definitions based on age 15 with secondary characteristics, age 13 without breast development, and three years after thelarche. Panel B: Evaluation flowchart beginning with physical examination of breast development and Tanner staging, progressing through laboratory tests (FSH, LH, prolactin, TSH), ultrasound, and karyotype analysis. Panel C: Anatomic classification of causes showing outflow tract (imperforate hymen, vaginal septum, Mullerian agenesis), ovarian (Turner, POI), pituitary (prolactinoma), and hypothalamic (functional, congenital) levels. Panel D: Comparative presentations of Turner syndrome (short stature, streak gonads), Mullerian agenesis (absent uterus, normal ovaries), and androgen insensitivity (46,XY, female phenotype, absent uterus).</image>

Section 7: Secondary Amenorrhea

Secondary amenorrhea is defined as the absence of menstruation for three months in a woman with previously regular cycles or for six months in a woman with previously irregular cycles. The critical first step in evaluation is a pregnancy test, as pregnancy is by far the most common cause of secondary amenorrhea in reproductive-age women. Secondary amenorrhea is a common clinical presentation with a broad differential diagnosis that includes endocrine, anatomic, and physiologic etiologies. The structured evaluation aims to identify the specific cause to guide appropriate management and to assess for associated health consequences of the underlying condition.

The differential diagnosis of secondary amenorrhea encompasses conditions at every level of the hypothalamic-pituitary-ovarian-uterine axis. After pregnancy, polycystic ovary syndrome is the most common cause and presents with anovulation, hyperandrogenism, and metabolic dysfunction. Hypothalamic amenorrhea results from physiologic or psychological stress, excessive exercise, or significant weight loss that suppresses gonadotropin-releasing hormone pulsatility. Hyperprolactinemia, whether from a prolactinoma or medications, inhibits gonadotropin secretion and can produce amenorrhea with or without galactorrhea. Premature ovarian insufficiency, defined as ovarian failure before age 40, presents with elevated gonadotropins and hypoestrogenism. Thyroid disease, both hypothyroidism and hyperthyroidism, disrupts normal menstrual cyclicity, and Asherman syndrome, caused by intrauterine adhesions from curettage or infection, represents an anatomic cause of amenorrhea.

The laboratory evaluation of secondary amenorrhea proceeds in a logical sequence to narrow the differential diagnosis. After a negative pregnancy test, serum follicle-stimulating hormone assesses ovarian function with elevated levels suggesting ovarian insufficiency and low or normal levels pointing toward hypothalamic or pituitary dysfunction. Prolactin level screens for hyperprolactinemia, and thyroid-stimulating hormone evaluates thyroid function. Serum estradiol provides information about the patient's estrogenic status, which has implications for bone health and cardiovascular risk. The combination of these results typically identifies the etiology or narrows the differential to guide further investigation.

The progestin challenge test provides functional assessment of estrogen status and outflow tract patency. Administration of medroxyprogesterone acetate for 7 to 10 days is followed by observation for withdrawal bleeding. A positive response with withdrawal bleeding indicates that adequate estrogen is present to stimulate the endometrium and the outflow tract is intact, pointing toward anovulation as the likely cause. Absence of withdrawal bleeding suggests either inadequate estrogen stimulation or outflow tract obstruction. The next diagnostic step when no bleeding occurs is to administer estrogen followed by progestin, known as the estrogen-progestin challenge. If bleeding occurs with this combination, the diagnosis is a low-estrogen state, while failure to bleed suggests outflow tract obstruction such as Asherman syndrome.

<image>Panel A: Diagnostic criteria for secondary amenorrhea showing 3-month criterion for regular cycles and 6-month criterion for irregular cycles with pregnancy test as the mandatory first step. Panel B: Differential diagnosis organized by anatomic level including hypothalamic (stress, exercise, weight), pituitary (prolactinoma), ovarian (PCOS, POI), thyroid (hypo- and hyperthyroidism), and uterine (Asherman syndrome) causes. Panel C: Laboratory evaluation sequence showing FSH, prolactin, TSH, and estradiol with interpretation of high FSH (ovarian insufficiency), low FSH (hypothalamic or pituitary), and elevated prolactin (hyperprolactinemia). Panel D: Progestin challenge test algorithm showing positive withdrawal bleed indicating anovulation, negative bleed followed by estrogen-progestin challenge, and interpretation of results for estrogen deficiency versus outflow obstruction.</image>

Section 8: Polycystic Ovary Syndrome

Polycystic ovary syndrome is diagnosed using the Rotterdam criteria, which require the presence of at least two of three cardinal features after exclusion of other causes of hyperandrogenism. The first criterion is oligo-ovulation or anovulation, manifesting as irregular or absent menstrual cycles. The second criterion is hyperandrogenism, which may be clinical (hirsutism, acne, androgenic alopecia) or biochemical (elevated total or free testosterone, dehydroepiandrosterone sulfate). The third criterion is polycystic ovarian morphology on ultrasound, defined as 12 or more antral follicles or an ovarian volume exceeding 10 milliliters. Importantly, other conditions that mimic polycystic ovary syndrome, including congenital adrenal hyperplasia, androgen-secreting tumors, Cushing syndrome, and thyroid disease, must be ruled out before the diagnosis is established.

The clinical features of polycystic ovary syndrome span reproductive, dermatologic, and metabolic domains, reflecting the systemic nature of this condition. Menstrual irregularity ranging from oligomenorrhea to amenorrhea is present in the majority of affected women and results from chronic anovulation. Hyperandrogenic manifestations include hirsutism affecting the face, chest, and abdomen, inflammatory acne, and male-pattern hair thinning. Metabolic features are highly prevalent and include central obesity, insulin resistance, and the metabolic syndrome with dyslipidemia and impaired glucose tolerance. Anovulatory infertility is a major reproductive consequence and represents one of the most common reasons patients with polycystic ovary syndrome seek medical attention.

Long-term health risks associated with polycystic ovary syndrome extend well beyond reproductive concerns and require ongoing surveillance. Type 2 diabetes develops at higher rates and at a younger age in women with polycystic ovary syndrome, necessitating regular glucose screening with either fasting glucose or oral glucose tolerance testing. The metabolic syndrome with its associated cardiovascular risk factors including hypertension, dyslipidemia, and central obesity increases the lifetime cardiovascular disease burden. Chronic anovulation exposes the endometrium to unopposed estrogen, significantly increasing the risk of endometrial hyperplasia and endometrial cancer. Obstructive sleep apnea is more common in women with polycystic ovary syndrome, particularly those with obesity, and should be screened for when suggestive symptoms are present.

Management of polycystic ovary syndrome is tailored to the patient's primary complaints and reproductive goals. Menstrual regulation is achieved with combined oral contraceptive pills, which also provide endometrial protection, or with cyclic progestins administered for 10 to 14 days each month. Hirsutism and acne respond to combined oral contraceptive pills and spironolactone, an androgen receptor blocker that must be used with reliable contraception due to its teratogenic potential. For women desiring fertility, letrozole is the first-line ovulation induction agent based on evidence of superior live birth rates compared to clomiphene citrate, with gonadotropins or in vitro fertilization reserved for refractory cases. Lifestyle modification including weight loss of as little as 5 to 10 percent of body weight can restore ovulatory cycles and improve metabolic parameters, and metformin may be used as an adjunct for insulin resistance.

<image>Panel A: Rotterdam diagnostic criteria diagram showing the three criteria (oligo-anovulation, hyperandrogenism, polycystic ovaries) with two of three required and the mandatory exclusion of mimicking conditions. Panel B: Clinical manifestation map showing reproductive features (irregular cycles, infertility), dermatologic features (hirsutism, acne, alopecia), and metabolic features (obesity, insulin resistance, metabolic syndrome). Panel C: Long-term health risk timeline showing screening recommendations for type 2 diabetes (regular glucose testing), cardiovascular risk (lipids, blood pressure), endometrial cancer (periodic biopsy if anovulatory), and sleep apnea. Panel D: Treatment algorithm organized by primary complaint showing menstrual regulation (OCP, cyclic progestins), hirsutism (OCP plus spironolactone), infertility (letrozole first-line, clomiphene, gonadotropins, IVF), and metabolic health (lifestyle, metformin).</image>

Section 9: Dysmenorrhea

Dysmenorrhea is classified into primary and secondary forms based on the presence or absence of underlying pelvic pathology. Primary dysmenorrhea refers to menstrual pain that occurs in the absence of identifiable pelvic disease and is caused by excessive prostaglandin production by the endometrium during menstruation. Secondary dysmenorrhea refers to menstrual pain caused by an underlying gynecologic condition and typically presents differently from primary dysmenorrhea in terms of onset, timing, and associated symptoms. The distinction between primary and secondary dysmenorrhea is clinically important because it determines the diagnostic evaluation and treatment approach.

Primary dysmenorrhea typically begins within 6 to 12 months of menarche, corresponding to the establishment of regular ovulatory cycles. The pain is characteristically suprapubic and crampy, begins with the onset of menstrual flow, and lasts 24 to 72 hours. The pathophysiology involves excessive release of prostaglandins, particularly prostaglandin F2-alpha, from the shedding endometrium, which causes intense myometrial contractions and ischemia. First-line treatment includes nonsteroidal anti-inflammatory drugs, which directly inhibit prostaglandin synthesis and are most effective when started at the onset of menses or even prophylactically, and hormonal contraception, which reduces prostaglandin production by thinning the endometrium and suppressing ovulation.

Secondary dysmenorrhea has multiple potential causes, each with characteristic features that help distinguish them from primary dysmenorrhea and from one another. Endometriosis, the most common cause of secondary dysmenorrhea, presents with chronic pelvic pain, dyspareunia, and infertility in addition to menstrual pain, and may be associated with pain that worsens over time. Adenomyosis causes progressive dysmenorrhea accompanied by heavy menstrual bleeding and an enlarged, tender uterus. Uterine fibroids may contribute to dysmenorrhea through mass effect and distortion of the uterine cavity, particularly when submucosal. Pelvic inflammatory disease presents with acute pain, fever, vaginal discharge, and cervical motion tenderness, while ovarian cysts may cause unilateral pain and may present with an adnexal mass on examination.

Evaluation for secondary dysmenorrhea is warranted when menstrual pain fails to respond to standard medical therapy, begins after years of painless menses, or is accompanied by features suggesting an underlying condition. Pelvic ultrasound is the initial imaging study and can identify fibroids, ovarian cysts, adenomyosis, and endometriomas. Physical examination may reveal tenderness, nodularity in the cul-de-sac suggestive of endometriosis, or an enlarged uterus consistent with fibroids or adenomyosis. Laparoscopy remains the gold standard for the definitive diagnosis of endometriosis when imaging is inconclusive and clinical suspicion remains high. Empiric treatment with hormonal therapy may be initiated before laparoscopy in many cases, with surgical evaluation reserved for patients who do not respond to medical management.

<image>Panel A: Primary versus secondary dysmenorrhea comparison showing onset timing (within 12 months of menarche versus later onset), pain character (suprapubic crampy versus variable), and pathophysiology (prostaglandins versus structural pathology). Panel B: Primary dysmenorrhea mechanism diagram showing endometrial prostaglandin F2-alpha release causing myometrial contraction and ischemia with NSAID and hormonal contraceptive treatment targets. Panel C: Secondary dysmenorrhea differential diagnosis showing endometriosis (chronic pain, dyspareunia), adenomyosis (heavy bleeding, enlarged uterus), fibroids (bulk symptoms), PID (fever, discharge), and ovarian cysts (unilateral mass). Panel D: Evaluation algorithm for refractory dysmenorrhea showing progression from pelvic examination and ultrasound through empiric hormonal therapy to laparoscopy for persistent symptoms with suspected endometriosis.</image>

Section 10: Premenstrual Disorders

Premenstrual syndrome encompasses a constellation of physical and emotional symptoms that occur during the luteal phase of the menstrual cycle and resolve with the onset of menses. Physical symptoms include abdominal bloating, breast tenderness, headache, fatigue, and fluid retention, while emotional symptoms include irritability, mood swings, and depressed mood. The diagnosis requires prospective documentation of symptoms over at least two menstrual cycles using a daily symptom diary, as retrospective recall is unreliable. The luteal phase timing is the hallmark diagnostic feature, distinguishing premenstrual syndrome from other mood or physical disorders that may worsen premenstrually but are present throughout the cycle.

Premenstrual dysphoric disorder represents a severe form of premenstrual symptomatology that meets specific diagnostic criteria defined in the DSM-5. The diagnosis requires the presence of at least five symptoms during the last week of the luteal phase, with at least one being a core mood symptom including marked affective lability, irritability or anger, depressed mood, or anxiety. Symptoms must resolve within a few days of the onset of menses and must cause clinically significant functional impairment in work, social activities, or relationships. The distinction from premenstrual syndrome is based on the severity of mood symptoms and the degree of functional impairment, with premenstrual dysphoric disorder representing the more debilitating end of the premenstrual symptom spectrum.

Treatment options for premenstrual disorders are selected based on symptom severity and the specific symptom profile. Lifestyle modifications including regular aerobic exercise, stress reduction techniques, and dietary changes form the foundation of management for mild symptoms. Calcium supplementation at 1200 milligrams daily and vitamin B6 have demonstrated modest benefit in clinical trials. Selective serotonin reuptake inhibitors are the most effective pharmacologic treatment for premenstrual dysphoric disorder and may be administered either continuously throughout the cycle or intermittently during the luteal phase only, with both regimens demonstrating comparable efficacy. Hormonal options include continuous combined oral contraceptive pills, and gonadotropin-releasing hormone agonists are reserved for severe refractory cases due to their significant hypoestrogenic side effects. Spironolactone may specifically address bloating and fluid retention symptoms.

Referral and additional support are indicated for patients with severe or refractory premenstrual symptoms. Patients meeting criteria for premenstrual dysphoric disorder who do not respond to first-line therapy with selective serotonin reuptake inhibitors should be referred for psychiatric consultation to confirm the diagnosis, exclude comorbid mood disorders, and consider alternative treatment approaches. Failed medical management after adequate trials of multiple agents should prompt reconsideration of the diagnosis and evaluation for alternative causes of the patient's symptoms. Any patient expressing suicidal ideation requires emergency psychiatric evaluation regardless of the suspected etiology, and clinicians should routinely screen for safety in patients with severe mood symptoms during the premenstrual period.

<image>Panel A: Premenstrual syndrome symptom timeline showing luteal phase onset, menstrual resolution, and the requirement for prospective diary documentation over at least two cycles with physical and emotional symptom categories. Panel B: DSM-5 diagnostic criteria for PMDD showing five required symptoms with at least one core mood symptom (affective lability, irritability, depressed mood, anxiety), luteal timing, and functional impairment requirement. Panel C: Treatment pyramid from lifestyle modifications (exercise, diet, calcium, B6) through SSRIs (continuous or luteal-only dosing) to hormonal therapy (continuous OCP, GnRH agonists) with efficacy ratings for each tier. Panel D: Referral criteria flowchart showing pathways for failed SSRI therapy leading to psychiatry consultation, failed multiple agents prompting diagnostic reassessment, and suicidal ideation requiring emergency evaluation.</image>

Summary

• The normal menstrual cycle spans 24 to 38 days with 4 to 8 days of flow and approximately 20 to 80 milliliters of blood loss, with ovulation occurring around day 14
• AUB evaluation begins with a pregnancy test and includes CBC, TSH, and ultrasound, with endometrial biopsy indicated for women over 45 or those with risk factors
• The PALM-COEIN system classifies AUB as structural (polyp, adenomyosis, leiomyoma, malignancy) or non-structural (coagulopathy, ovulatory, endometrial, iatrogenic, not classified)
• Fibroid management ranges from medical therapy (hormonal agents, tranexamic acid) to surgical options (myomectomy, ablation, hysterectomy) based on symptoms and fertility goals
• Primary amenorrhea is defined as absence of menses by age 15 with secondary sexual characteristics or by age 13 without breast development
• Secondary amenorrhea requires 3 to 6 months of absent menses, with pregnancy as the most common cause and PCOS as the most common non-pregnant etiology
• PCOS is diagnosed by the Rotterdam criteria requiring 2 of 3 features (oligo-anovulation, hyperandrogenism, polycystic ovaries) and carries increased endometrial cancer risk
• Primary dysmenorrhea is prostaglandin-mediated and responds to NSAIDs and hormonal contraception as first-line therapies
• PMS is distinguished from PMDD by the severity of mood symptoms and the degree of functional impairment
• PMDD treatment includes SSRIs administered continuously or during the luteal phase only, with comparable efficacy for both regimens

Key Terms

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