As with other medical conditions, the patient should undergo a complete history and physical exam. Common presenting complaints include menstrual irregularity and various symptoms of hypoestrogenism. These include hot flushes and genital atrophy. In the early phase of POF, menstruation may remain regular and the patient may present with infertility. In these cases, the diagnosis is made on the basis of elevated levels of gonadotropins only, as the remainder of the history and physical findings will be normal.

The patient may have a prior history of ovarian surgery, especially if multiple interventions for endometrioma removal were performed. Past history of treatment for malignancies including chemotherapy and/or radiation predispose the patient to POF. There may also be a family history of POF, because up to 10% of cases of POF may be familial.

Physical examination may reveal the stigmata of Turner’s syndrome, including short stature, shield chest, wide carrying angle or low posterior hairline. There may be signs of other autoimmune diseases, such as a goiter, suggestive of autoimmune thyroiditis, or increased skin pigmentation, consistent with adrenal insufficiency. There may be signs of hypoestrogenism, such as atrophic vaginitis.

The laboratory evaluation should rule out other causes of oligomenorrhea, and should include serum levels of prolactin, thyroid-stimulating hormone (TSH), and human chorionic gonadotropin (hCG). Elevations of FSH are characteristic of the condition. In the past, a specific value (such as 20 mIU/mL or 40 mIU/mL) was used as a diagnostic criterion. However, FSH levels vary widely among laboratories and thus, no specific value is used. However, the patient with POF should have an FSH level which is above the normal range. Women with residual ovarian function should have FSH levels measured on the third day of menstrual bleeding. This is because follicular development may occur in response to the elevated FSH, and the resulting high estradiol levels produced by the granulosa cells will act to decrease FSH levels, resulting in a false-negative evaluation. It has been observed that women with early follicular phase FSH levels as high as 60 mIU/mL may continue to have normal menstrual cycles, and even continue to ovulate. Normal-appearing oocytes have been retrieved from such cycles and fertilization in vitro was achieved. However, none of the embryos implanted. Serum FSH levels are higher than those of luteinizng hormone (LH); this observation may be used to differentiate POF from a mid-cycle gonadotropin surge, in which LH levels are higher than those of FSH.