A medical history and physical examination should be performed that is directed toward eliciting any symptoms or signs of hyperandrogenism. Screening laboratory tests for hyperandrogenism include a serum DHEAS, total testosterone, free testosterone, and luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio. These tests should be obtained apart from the time of ovulation in order to avoid the surge of hormones associated with ovulation. From a practical standpoint, it may be easiest to suggest that women have these tests performed either just prior to or during the menstrual period. It is important to note that if a patient is on oral contraceptives at the time of hormonal testing, an underlying hyperandrogen-emia maybe masked. This does not occur with antiandrogens such as cyproterone or spironolactone. Therefore, it is best that patients discontinue oral contraceptives four to six weeks prior to the endocrine evaluation.
Excess androgens may be produced by either the adrenal gland or the ovary. Serum levels of DHEAS can be used to screen for an adrenal source of excess androgen production. Patients with a serum DHEAS greater than 8000 ng/mL (units may differ depending upon the laboratory) may have an adrenal tumor and should be referred to an endocrinologist for further evaluation. Some adrenal tumors may also produce testosterone. Values of DHEAS in the range of 4000 ng/mL to 8000 ng/mL may be associated with congenital adrenal hyperplasia, which is most commonly due to a partial deficiency in the 21-hydroxylase or 11-hydroxylase enzyme in the adrenal gland.
Such an enzyme deficiency results in the shunting of steroids from the cortisol biosyn-thetic pathway into the androgen biosynthetic pathway.
An ovarian source of excess androgens can be suspected in cases where the serum total testosterone is elevated. Serum total testosterone in the range of 150ng/dL to 200ng/dL or an increased LH/FSH ratio (greater than 2 to 3) can be found in cases of polycystic ovary disease. This condition is a spectrum and is often, but not always, associated with irregular menstrual periods, reduced fertility, obesity, insulin resistance, or hirsutism. Greater elevations in serum testosterone may indicate an ovarian tumor and appropriate referral should be made. In some cases, there can be modest elevations in both DHEAS and testosterone. A serum level of 17-hydroxypregneneolone can be obtained to discern between an ovarian or adrenal source of androgens. If 17-hydroxypregneneolone is elevated, it indicates an adrenal source of excess androgens, most often secondary to late onset congenital adrenal hyperplasia. Of note is that there is a significant amount of variation in an individual's serum androgen levels. In cases where abnormal results are obtained, it is recommended to repeat the test before proceeding with therapy or a more extensive work-up.
Questions arise as to the importance of a pelvic ultrasound in the diagnosis of polycystic ovarian syndrome. This test can be nonspecific, in that women with normal androgens may have ovarian cysts and conversely, women with hyperan-drogenism and other findings associated with polycystic ovarian syndrome may not have ovarian cysts at the time of pelvic ultrasound. For this reason, the diagnosis of polycystic ovarian syndrome is more heavily based upon the serum hormonal profile and associated clinical findings.
In the majority of women with acne, serum androgens are completely normal, yet these women will in fact respond if treated with hormonal therapy. Studies have shown that, as a group, women with acne may have higher levels of serum DHEAS, testosterone, and DHT than those without acne (7,34). However, although higher, these laboratory values may still be within the normal range. Serum levels of DHEAS, DHT, and IGF-1 are reported to correlate positively with acne lesion counts in women, whereas androstenedione and DHEAS correlate with lesion counts in men (35). Reduction of serum androgens or inhibition of their action, as obtained with oral contraceptives or antiandrogens, respectively, can lead to improvement in acne in women with normal serum androgen levels.
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