Diagnostic Evaluation and Management of Menstrual Irregularities

Initial Assessment and Diagnosis

A pregnancy test should be performed to rule out pregnancy as a cause of missed periods, as recommended by the American College of Obstetricians and Gynecologists 1
A detailed menstrual history should be obtained, including age of menarche, regularity of menses, duration and amount of bleeding, presence of intermenstrual bleeding, use of medications that could affect menstruation, other health issues, and family menstrual history, as recommended by the British Journal of Sports Medicine guidelines 2
Physical examination should include BMI calculation, signs of hyperandrogenism (hirsutism, acne), thyroid examination, and abdominal/pelvic examination if sexually active, as recommended by the American Academy of Family Physicians 3
A baseline hormonal panel, including FSH, LH, estradiol, prolactin, and TSH, should be ordered, as suggested by the Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists 4, 5

The following laboratory tests are recommended for diagnosis and monitoring of PCOS:

Laboratory Test	Abnormal Level
Prolactin	>20 μg/l
Progesterone	<6 nmol/l
Testosterone	>2.5 nmol/l
Androstenedione	>10.0 nmol/l
DHEAS	Age 20-29 >3800 ng/ml, Age 30-39 >2700 ng/ml
Fasting glucose/insulin	Fasting glucose >7.8 mmol/l, Glucose/insulin ratio >4
LH/FSH ratio	>2
FSH	>35 IU/l
LH	>11 IU/l or <7 IU/ml

Combined hormonal therapy, such as transdermal 17β-estradiol with cyclic oral progestin, is recommended for PCOS patients to regulate menstrual cycles and reduce androgen levels, as suggested by the American College of Obstetricians and Gynecologists 6
Metformin is recommended as a first-line treatment for insulin resistance in PCOS, improving insulin sensitivity, reducing androgen levels, and restoring regular menstrual cycles, with a starting dose of 500mg daily, gradually increasing to 1500-2000mg daily in divided doses, as recommended by the American Diabetes Association 6, 7
Lifestyle modifications, including weight loss and 150 minutes of moderate-intensity exercise weekly, can improve menstrual regularity and are recommended by the Endocrine Society 6, 5, 7
Hormone replacement therapy (HRT) with transdermal 17β-estradiol and cyclic oral progestin, as well as calcium and vitamin D supplementation for bone health, is recommended for patients with primary ovarian insufficiency, as suggested by the American College of Obstetricians and Gynecologists 8

Regular monitoring of androgen levels, menstrual cycle regularity, and symptoms of hyperandrogenism is essential for PCOS management, with reassessment every 3 months, as recommended by the American Diabetes Association and the American College of Cardiology 6, 7, 9
Annual screening for type 2 diabetes and cardiovascular risk assessment is recommended for women with PCOS, as they are at increased risk for these conditions, with a high strength of evidence 8
Gynecology referral is warranted for patients with suspected anatomic abnormalities, persistent symptoms despite normal laboratory values, or desire for fertility assessment, as recommended by the American College of Obstetricians and Gynecologists 10, 8
Endocrinology referral is recommended for patients with elevated FSH levels, suspected PCOS with metabolic concerns, or suspected chromosomal abnormalities, according to the American Association of Clinical Endocrinologists 8

Low energy availability can disrupt LH pulsatility and cause functional hypothalamic amenorrhea, particularly in athletes or those with recent weight changes, as suggested by the British Journal of Sports Medicine 2
Irregular periods can cause anxiety about fertility and normalcy, and screening for disordered eating, excessive exercise, or body image concerns is recommended, as suggested by the British Journal of Sports Medicine 2
Overlooking eating disorders or energy deficiency, particularly in athletes or patients with weight concerns, can lead to long-term bone health issues if untreated, as suggested by the British Journal of Sports Medicine 2
For hypothalamic dysfunction, addressing underlying stressors, ensuring adequate nutrition and energy intake, and considering hormonal therapy if bone health concerns are present is recommended, as suggested by the British Journal of Sports Medicine 2
For thyroid or prolactin abnormalities, treating the underlying endocrine disorder is essential, as recommended by the American Academy of Family Physicians 3