Laboratory Studies

Laboratory evaluation in patients with anovulation includes the following:

Pregnancy test - Quantitative beta-HCG in all women of reproductive age
FSH - Important in assessing for premature ovarian failure
LH - In combination with FSH, helps establish a diagnosis of PCOS (with LH/FSH ratio >2:1)
Ovarian steroid hormones - Estradiol, progesterone (midluteal)
TSH - Hypothyroidism
Prolactin - Hyperprolactinemia
Glucose - Using a 2-hour glucose tolerance test after 75-g glucose load
Cortisol with or without ACTH stimulation test - Helps determine presence of adrenal insufficiency
Total testosterone/free testosterone - In the presence of hirsutism or virilization, can help distinguish ovarian versus adrenal origin
Dehydroepiandrosterone sulfate (DHEAS) - Hirsutism or virilization of adrenal origin
17-Hydroxyprogesterone - CAH
Pregnenolone - 17-alpha-hydroxylase deficiency

Workup for autoimmune disorders may be considered when initial test results are uninformative and may include the following studies:

Complete blood count (CBC)
Complete metabolic profile - Electrolytes, albumin, renal function tests, liver function tests
Antinuclear antibodies
Rheumatoid factor
Erythrocyte sedimentation rate
C-reactive protein
Thyroid antibodies

Other tests may include the following:

Karyotype - Usually performed in patients younger than 30 years to rule out presence of Y chromosome (frequency of germ cell tumors in patients >30 y is negligible)
Galactose-1-phosphate - Galactosemia

Imaging Studies

Radiologic studies in the evaluation of patients with anovulation includes the following:

Ultrasonography - Evaluation of ovaries and endometrium (transvaginal), adrenals (abdominal). Evaluate for the presence of 12 or more follicles in each ovary measuring 2-9 mm in diameter and/or increased ovarian volume greater than 10 mL.^[13]A thickened heterogeneous endometrium in the setting of chronic anovulation should prompt suspicion for endometrial hyperplasia regardless of the patient's age.
Computed tomography scanning - Adrenals (abdominal)
Magnetic resonance imaging - Pituitary glands, adrenals
Bone density scanning (ie, dual-energy x-ray absorptiometry [DEXA scan]) - Vertebrae and femur (primarily in hypoestrogenic states)
Nuclear thyroid scanning - Hot versus cold nodules in the presence of positive physical findings and symptoms

Procedures

Endometrial biopsy may be performed to exclude endometrial hyperplasia. An endometrial biopsy should be performed in all women older than 35 years who have irregular uterine bleeding, whether in the presence of anovulatory or ovulatory cycles. Biopsy is also indicated in women younger than 35 years who have a long-standing history of anovulation and concomitant risk factors for endometrial hyperplasia, such as obesity (unopposed estrogenic environment). The most important aspect is that age should not be a factor in deciding whether to perform an endometrial biopsy.

Histologic Findings

Endometrial glands undergo mild architectural changes, including cystic dilation reminiscent of a proliferative endometrium, because of prolonged, excessive endometrial stimulation by estrogens. Unscheduled breakdown of the stroma may also occur, with no evidence of the endometrial secretory activity usually observed as a result of a functioning corpus luteum and subsequent production of progesterone.

Treatment & Management

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Media Gallery

Anovulation. Polycystic ovary. Courtesy of Jairo E. Garcia, MD.
Anovulation. On the left is an unaffected patient aged 12 years. On the right is the same patient aged 13 years after developing Cushing disease.
Anovulation. Left adrenal mass discovered incidentally.
Anovulation. MRI showing a nonenhancing area in the pituitary consistent with a microadenoma in a patient with hyperprolactinemia.