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Although androgen excess can manifest in many ways, the most common and recognizable symptoms are hirsutism and acne. Reports of hirsutism and acne should be taken seriously because of their possible association with medical disorders, their substantial effect on self-esteem and quality of life, and the potential for psychosocial morbidity. In patients with symptoms of androgen excess, the differential diagnosis should include physiologic hyperandrogenism of puberty, idiopathic hyperandrogenism, and polycystic ovary syndrome (PCOS). There is a great deal of overlap between the symptoms of PCOS and those of normal puberty, which makes the diagnosis of PCOS in the adolescent difficult. Treatment of acne and hirsutism should not be withheld during the ongoing longitudinal evaluation for possible PCOS. On physical examination, body mass index, blood pressure, and signs of hyperandrogenism, such as acne and hirsutism, should be evaluated. Although guidelines differ on recommended laboratory studies, most include measurement of total testosterone, free testosterone, or both, and screening for nonclassic congenital adrenal hyperplasia with a 17-hydroxyprogesterone test. Elevation of the free or total testosterone level higher than the adult female normative values is a key diagnostic feature of biochemical hyperandrogenism. Because treatment is indicated only when symptoms are distressing to the patient, the degree to which acne or hirsutism bothers the patient should be assessed. Before initiation of any medical therapy, expectations of treatment should be discussed with the patient. Anticipatory guidance is critical to help patients understand the timeline for expected responses to therapy.

Background: Familial partial lipodystrophy, Dunnigan variety, is a rare autosomal dominant disorder caused by missense mutations in LMNA gene. Individuals are predisposed to insulin resistance and its complications, including features of polycystic ovary syndrome., Case: A 27-year-old Hispanic woman presented with oligomenorrhea and hirsutism. Examination revealed cushingoid facies, significant hirsutism, acanthosis nigricans, and a lean body habitus. Metabolic testing identified diabetes mellitus, dyslipidemia, and steatohepatitis. A diagnosis of familial partial lipodystrophy, Dunnigan variety, was confirmed by the detection of a heterozygous p.Arg482Trp (c.1444C>T) missense mutation in the lamin A/C (LMNA) gene. Subsequently, seven female relatives were diagnosed with familial partial lipodystrophy, Dunnigan variety, four of whom had menstrual irregularities., Conclusion: Familial partial lipodystrophy, Dunnigan variety, can present with features similar to polycystic ovary syndrome. Diagnosis is critical because the metabolic complications of the disorder have significant morbidity.

Hirsutism is the presence of terminal (coarse) hairs in females in a male-like pattern, affecting between 5% and 15% of women, depending on definition. Hirsutism has a significant negative impact on psychosocial development and is usually a sign of an underlying endocrine abnormality-namely, androgen excess. The most common cause of androgen excess is the polycystic ovary syndrome (PCOS), with 21-hydroxylase-deficient nonclassic adrenal hyperplasia, the hyperandrogenic insulin-resistant acanthosis nigricans syndrome, androgen-secreting tumors, and androgenic drug intake occurring less frequently. However, although 70-80% of patients with androgen excess demonstrate hirsutism, this sign may be less prevalent among women of Asian extraction. Conversely, not all hirsute patients have evidence of detectable androgen excess, as 5-15% of these women have "idiopathic hirsutism," with normal ovulatory function and androgen levels. There is a strong familial predilection for hirsutism, primarily because the underlying endocrine disorders (eg, PCOS) and the factors regulating the development of hair growth (eg, androgen receptor activity, 5alpha-reductase activity) have a strong genetic component. The diagnostic evaluation of the potentially hirsute patient first involves confirming the presence of hirsutism and then excluding associated or etiological abnormalities and disorders (eg, ovulatory dysfunction, adrenal hyperplasia, diabetes, thyroid hormone abnormalities). Treatment should be undertaken using combination therapy, to possibly include 1) hormonal suppression (oral contraceptives, long-acting gonadotropin-releasing hormone analogues, and insulin sensitizers), 2) peripheral androgen blockade (spironolactone, flutamide, cyproterone acetate, or finasteride), and 3) mechanical/cosmetic amelioration and destruction of the unwanted hairs (electrology and, potentially, laser hair removal). The application of eflornithine hydrochloride 13.9% topical cream may also be useful to ameliorate unwanted facial hair growth. Overall, although hirsutism is a frequent and distressing abnormality often signaling an underlying endocrine disorder, a systematic approach to evaluation will uncover the etiology, and combination therapy will provide satisfactory treatment for most patients.

Background: The androgen source in women with hirsutism and signs of virilism may be the ovary or adrenal gland., Cases: Three patients with androgen excess are reported. Two had hyperandrogenemia and Cushing syndrome with an adrenal mass greater than 5.5 cm; the third had a small adrenal adenoma secreting only testosterone and responsive to human chorionic gonadotropin. In all cases, the pathologic report from surgery and the long-term resolution of symptoms confirmed the benign nature of the tumors., Conclusion: Basal and dynamic hormonal tests cannot precisely differentiate ovarian from adrenal tumors. Adrenal adenomas must be considered as a cause of hyperandrogenic syndrome.

Background: Hormone production is a characteristic associated with the presence of solid tumors in the ovary. We present a case of a solitary ovarian cyst producing large amounts of testosterone and presenting with rapid onset of hirsutism., Case: A woman presented approximately 6 months postpartum with irregular menses and rapid onset of hirsutism. Laboratory and radiologic evaluation indicated an ovarian cyst as the source. On removal, the cyst was found to have high amounts of testosterone in its fluid and the surrounding stroma had nests of luteinized cells., Conclusion: The chronic anovulation in the postpartum period may have prolonged the lifespan of the luteinized stromal cells, resulting in high levels of circulating testosterone and causing rapid progression of hirsutism.

Marked improvement in the severe hypertension (250/150 mmHg) and hirsutism of a patient suffering from polycystic ovary syndrome was quickly achieved by the use of spironolactone 200 mg per day. Substitution of spironolactone with bromocriptine induced further amelioration of these symptoms and renewal of ovulatory cycles. These drugs may afford another mode of therapy in patients with polycystic ovary syndrome.

Thirty adult patients with gonadal dysgenesis were identified over the five-year period between January 1981 and December 1985 in the Reproductive Endocrinology and Infertility Clinic at the University of Southern California/Los Angeles County Medical Center. Six patients had previous menstrual function and presented with secondary amenorrhea. Chromosome analysis revealed three patients with 45,X karyotypes and three patients with 45,X mosaics. One of these patients (45,X/47,XXX) presented with secondary amenorrhea and elevated follicle-stimulating hormone, and conceived twice after being placed on estrogen replacement therapy. Three additional patients presented with hirsutism as their primary complaint, and had karyotypes of 45,X/46,XY, 45X/46X,i(Yq), and 45,X. The latter patient, who had her karyotype confirmed by analysis of four tissue sources, had a streak gonad and a dysgenetic gonad, with both follicles and seminiferous tubules.

Five new patients with postmenarchial onset of adrenal virilism related to 21-hydroxylase deficiency are presented. Diagnostic criteria are reviewed. Four pregnancies resulting in 3 term infants occurred after instigation of therapy. Eleven patients similar in clinical presentation are reviewed for comparison. Findings of value in distinguishing these two groups of patients are discussed.

A case of mucinous cystadenoma associated with androgen secretion is presented to add to the growing body of literature concerning hormone secretion by ovarian neoplasms regarded as "nonfunctional." The theorized mechanisms of hormone production in these tumors also are reviewed.

The authors report the case of a 23-year-old woman with a virilizing lipoid cell tumor of the ovary. The patient developed precocious puberty at age 4 and from age 5 to 10 years was treated weekly with intramuscular medroxyprogesterone acetate. She began to menstruate spontaneously at age 13, but developed hirsutism, acne, and irregular menses at age 15 followed by secondary amenorrhea at age 20. Steroid analyses demonstrated elevated peripheral plasma levels of testosterone, dihydrotestosterone, androstenedione, 17 alpha-hydroxyprogesterone, progesterone, desoxycorticosterone, estrone, and estradiol. Catheterization of the adrenal and ovarian veins revealed increased secretion of testosterone, dehydroepiandrosterone, androstenedione, 17 alpha-hydroxyprogesterone, progesterone, desoxycortcosterone, and corticosterone, 11-desoxycortisol, cortisol, estrone, and estradiol from the right ovarian vein. At surgery a right ovarian lipoid cell tumor was removed. Incubation studies with the tumor tissue confirmed the presence of gonadal and adrenocortical steroids. The tissue also contained high-affinity human chorionic gonadotropin-luteinizing hormone binding sites with normal binding affinity.

A 21-year-old white woman presented with virilization, hirsutism, and acne of 1.5 years' duration. Endocrine testing demonstrated complete suppression of serum testosterone, from 5.3 to 0.6 ng/mL, and serum androstenedione, from 4.7 to 1.7 ng/mL, after oral administration of 50 micrograms of mestranol and 1 mg of norethindrone for 21 days. No suppression of either steroid was produced by dexamethasone, whereas serum dehydroepiandrosterone sulfate was suppressed from 5.2 to 1.9 micrograms/mL. A left salpingo-oophorectomy was performed for a 3 x 4-cm Sertoli-Leydig cell tumor of intermediate differentiation. Intraoperative studies demonstrated that the tumor secreted testosterone, androstenedione, 17 alpha-hydroxyprogesterone, and estradiol, but not dehydroepiandrosterone sulfate. These findings support the thesis that hormonal manipulation tests cannot differentiate between adrenal and ovarian virilizing tumors. Nor does the oral contraceptive suppression of testosterone secretion exclude an ovarian malignancy. The patient remains free of recurrence after 7 years.

Clinical evidence of adrenal androgen hyperfunction (premature pubarche, hirsutism, amenorrhea) occurred in the studied proband, her mother, maternal aunt (twin sisters), and maternal great-grandmother. The basal levels of androgen in the first three were variably elevated. In all the members of this family who were tested, the response of 17-hydroxyprogesterone and progesterone to adrenocorticotropic hormone stimulation was either normal or of the type seen in heterozygotes for congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Of particular importance is the fact that neither the proband nor her mother or maternal aunt had the type of response seen in homozygotes presenting the attenuated form of congenital adrenal hyperplasia. The disorder appears to be a familial condition resulting in excessive levels of adrenal androgens beginning during childhood years, causing hirsutism and amenorrhea and interfering with normal pubertal and adult ovarian function. Glucocorticoid therapy suppresses adrenal androgen levels; in two individuals, conception occurred twice in each during such treatment in otherwise amenorrheic individuals. The pattern of transmission of the disorder appears to be either autosomal or X-linked dominant, and not linked to the homologous leucocytic antibodies (HLA) region of the sixth chromosome.

A case of recurrent androgenicity associated with pregnancy is described. The patient is a 32-year-old black woman with hirsutism and irregular menses who developed elevated androgen levels in the male range during a pregnancy, with remission after delivery. A recurrence of the elevated androgen levels was noted during a subsequent pregnancy, again with remission after a termination. We have analyzed the possible etiologic mechanisms underlying this condition and reviewed the literature of similar cases.

Blood samples were obtained from 145 preovulatory and postovulatory hirsute women and the plasma was analyzed for total testosterone (T), T index, and free T concentration as well as the fraction of free T percentage and that bound by testosterone-estradiol binding globulin. Fifty-six patients were subjected to a 2-week dexamethasone (DXM) suppression test to delineate the source of androgen excess. Presuppression and postsuppression samples were also analyzed for plasma T concentrations and its free and bound fractions. The total T, T index, and free T were elevated in 58, 66, and 55% of hirsute women, respectively. The percentage of bound T fraction was decreased in only 39% of hirsute women, whereas the percentage of free T fraction was increased in 30% and decreased in 11% of hirsute women. The postovulatory hirsute women had a normal percentage of free and bound T fractions, although their total plasma concentrations were elevated. They also had a lower frequency of abnormal levels in all T measurements than preovulatory hirsute women. The DXM seems to deplete the plasma binding globulin; thus the bound T fractions in the post-DXM samples were lower than the pre-DXM values. The total T may be a better measure than the free T values in evaluation of the DXM suppression test for hirsute women.

A group of 51 women with a diagnosis of polycystic ovary syndrome (PCO) were investigated. They were further classified into PCO Type I and PCO Type II based on clinical and laboratory investigations. Serum levels of unbound (free) and total testosterone, testosterone binding globulin (TBG), and androstenedione were measured in these women and compared with values in normal women. Mean levels of all these steroids were elevated in women with PCO. No difference in adrogen levels was found between women with PCO Type I and PCO Type II. Serum unbound testosterone concentrations correlated better with the presence and severity of hirsutism than did the total testosterone.

A case of ovarian Brenner tumor displaying androgenic activity and clinical masculinization is reported in a 65-year-old woman. Plasma androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone, dihydrotestosterone, cortisol, estradiol, FSH, LH, and prolactin were measured before and after suppression with dexamethasone and stimulation with hCG, and again after removal of the tumor. The plasma androgenic compounds were measured in both ovarian and peripheral veins. Basal levels of androstenedione and of total testosterone were significantly elevated, decreasing to normal ranges after operation and remaining after 3 months. There was a sharp increase of total testosterone, DHEAS, and dihydrotestosterone levels after administration of hCG. The levels of androstenedione, DHEAS, testosterone, and dihydrotestosterone were higher in the ovarian vein than in the peripheral vein. These findings indicate that the tumor was the main source of these androgenic hormones.

Four women with phenotypic features of Turner's syndrome and with poly cystic ovaries (PCO) are describe. In addition to the phenotypic features, Case 1 had primary amenorrhea and small PCO, Case 2 had a 46, XX/45, X karyotype (lumphocytes), Case 3 had enlarged PCO which contained a decreased number of oocytes, and Case 4 had enlarged PCO and was short in statute. These cases support the concept of a relation between PCO and the X chromosome. Some PCO may represent an intermediate condition in a spectrum that extends from the streak gonad of Turners syndrome to the normal ovary. Evidience for X chromosome involvement in PCO is summarized. The concept is advanced that at least some cases of OCO may be due to X chromosomal factors causing an abnormal follicular appartus.