Hirsutism,help?

Question

My sister has hirsutism in her face & has masculine her distribution,but light hair,not so thick radiating towards the umbilicus & in the inner asoect of her thighs & I want to help her.Don't tell me do acu-light laser her removal as the condition is generalized & laser will cost her alot of money.She took DIANE-35 a drug which contained cyproterone acetate & ethinylestradiol 3 years ago & it was giving excellent results,but this drug is no longer for sale.I asked in a phamacy & they said ethinyl estradiol alone is enough but I don't believe them cause here people who work in pharmacy know nothing about drugs,So if you please tell me a trade name of a drug that contains both cyproterone acetate & ethinylestradiol,I'll be grateful.

Answer 1

Hirsutism, also see Idiopathic Hirsutism Below

INTRODUCTION — Polycystic ovary syndrome (PCOS) is the most common cause of infertility in women [1], and is primarily characterized by ovulatory dysfunction and hyperandrogenism. The diagnosis of PCOS has life-long implications with increased risk for infertility, metabolic syndrome, type 2 diabetes mellitus, and possibly cardiovascular disease. It should be considered in any adolescent girl with hirsutism, persistent acne, menstrual irregularity, or obesity.

The clinical manifestations and diagnosis of PCOS in adolescents are presented here. The definition, pathogenesis, and treatment of PCOS in adolescents are discussed separately. (See "Definition, pathogenesis, and etiology of polycystic ovary syndrome in adolescents" and see "Treatment of polycystic ovary syndrome in adolescents").

CLINICAL FEATURES — It is important to appreciate that PCOS is a syndrome, not a disease, reflecting multiple potential etiologies and variable clinical presentations. Adolescent girls with PCOS may present with hirsutism, menstrual irregularities, obesity, acanthosis nigricans, premature pubarche, and/or precocious puberty (show figure 1). Any one of these findings may be the sole feature of the syndrome. Treatment-resistant acne, scalp hair loss, seborrhea, or hyperhidrosis also may be presenting chief complaints.

Hirsutism — Hirsutism is defined clinically as excessive sexual hair that appears in a male pattern [2]. Hirsutism is commonly graded according to the Ferriman-Gallwey system, which quantitates the extent of hair growth in the most androgen-sensitive areas (show figure 2). In adult women, a score of <8 is normal, 8 to 15 indicates mild hirsutism, and >15 indicates moderate to severe hirsutism.

Hirsutism must be distinguished from hypertrichosis, the generalized excess growth of hair that sometimes occurs on a hereditary basis, or in patients taking glucocorticoids, phenytoins, diazoxide, or cyclosporine. Hypertrichosis is distributed in a nonsexual pattern (eg, generalized distribution or more prominent distribution on the forehead or shoulders) and is not caused by excess androgen, although it may be aggravated by excess androgen.

Acne vulgaris, pattern alopecia, seborrhea, hyperhidrosis, and hidradenitis suppurativa are considered to be hirsutism equivalents [3]. Hyperandrogenism should be considered in adolescent females who have inflammatory acne that is unusual in its age of onset (before midpuberty), severity, persistence, or unresponsiveness to standard therapy.

Hirsutism and hirsutism equivalents are variably expressed manifestations of excess androgens that are present in approximately two-thirds of hyperandrogenic females [2,3]. The absence of hirsutism in approximately one-third of hyperandrogenic women appears to be because of relatively low sensitivity of their pilosebaceous unit to androgens. In addition, hirsutism may be absent in young adolescents whose hyperandrogenism has not evolved fully.

Not all hirsutism is caused by hyperandrogenism. Approximately one-half of mildly hirsute women and one-sixth of moderately hirsute women do not have androgen excess, but have idiopathic hirsutism. (See "Evaluation of women with hirsutism").

Ovarian findings

Polycystic ovaries — Although PCOS in adolescents has clinical and endocrine features similar to those in adults, the detection of polycystic ovaries with ultrasonography appears to be less sensitive in adolescents (show radiograph 1) [3]. In a comparison of consecutively studied hyperandrogenic females, polycystic ovaries were found in 55 percent of adolescents and 75 percent of adults. This difference, however, may reflect the limitation of imaging virginal adolescents by the abdominal route compared with the higher-definition transvaginal route used in adults. A polycystic ovary may not develop until two or more years after menarche [4]. In adolescents, it also is difficult to distinguish by ultrasonography a polycystic ovary from a multicystic ovary, a normal adolescent variant. (See "Ultrasonography" below).

Anovulation — Approximately two-thirds of patients with PCOS, whether adolescent or adult, have anovulatory symptoms. These symptoms vary and include:

Primary amenorrhea
Oligomenorrhea or secondary amenorrhea (less than nine periods per year)
Dysfunctional uterine bleeding defined by excessive or irregular bleeding at intervals of less than 22 days
Normal menstrual cyclicity does not necessarily signify ovulatory cycles; anovulatory cycles are suggested by the lack of moliminal symptoms (eg, breast tenderness and dysmenorrhea). A subset of anovulatory patients may have infrequent ovulation (oligoovulation). Chronic anovulation is associated with increased risk of developing endometrial hyperplasia and carcinoma. (See "Clinical features and diagnosis of endometrial cancer", section on Risk factors).

In the adolescent, it is difficult to initially distinguish PCOS from physiologic anovulation, which normally occurs in approximately one-half of menstrual cycles in the first two years after menarche [5]. Adolescents who have irregular menstrual cycles have higher plasma androgens than do those who have regular menstrual cycles. One-third of these patients have androgen levels that are greater than those in normal adults [6]. Girls whose irregular cycles continue for two years after menarche have a two-thirds probability of ongoing menstrual irregularity [7]. During this time period, an individual's androgen levels are established, so that once hyperandrogenemia develops, it usually persists [8]. Thus a high androgen level in an adolescent with irregular menses strongly suggests a diagnosis of PCOS, even in the absence of other clinical features of the syndrome. Although functional ovarian hyperandrogenism of PCOS is often present near the onset of menarche, it sometimes cannot be documented until later (up to three years) after the onset of menarche [9].

Obesity — Obesity, present in approximately one-half of patients with PCOS, often is the initial complaint. It is unclear how often obesity presents as the only clinical feature. PCOS is the single most common endocrine obesity syndrome in females. The obesity occasionally begins in mid-childhood. It typically is central (android) in type. In adult women, a waist circumference 88 cm defines abdominal obesity and is a criterion for the metabolic syndrome as defined by the National Heart, Lung, and Blood Institute/American Heart Association [10]. A waist circumference 88 cm is approximately the 85th percentile for American girls who are 13 years of age [11,12]. Even normal-weight females with PCOS are reported to have a body fat content that is 50 percent greater than normal [13]. (See "The metabolic syndrome (insulin resistance syndrome or syndrome X)").

Manifestations of insulin resistance — Insulin resistance is common in patients with PCOS, and clinical manifestations include acanthosis nigricans and the metabolic syndrome.

In addition, rare clinical manifestations of severe insulin resistance in PCOS include pseudo-Cushing's syndrome [14] and pseudo-acromegaly [15]. These may begin prepubertally and precede the development of PCOS [16]. (See "Definition, pathogenesis, and etiology of polycystic ovary syndrome in adolescents", section on Insulin resistance).

Acanthosis nigricans — Acanthosis nigricans is an indicator of insulin resistance, and may be the presenting complaint of patients with PCOS [17]. (See "Metabolic and inherited diseases affecting the skin", section on Acanthosis nigricans).

Metabolic syndrome — The metabolic syndrome is a cluster of critical levels of abdominal obesity, blood pressure, serum triglycerides, HDL cholesterol, and glucose. Three or more of these findings confer a high risk of cardiovascular disease [10]. These patients have insulin resistance. In our center, 25 percent of adolescents with PCOS had metabolic syndrome [18]. This prevalence was three times greater than expected for age, ethnicity, or body mass index.

Premature pubarche and precocious puberty — Premature pubarche (appearance of sexual hair before 8 years of age) and, to a lesser extent, early breast development (before 8 years of age) seem to be risk factors for, or predecessors of, PCOS [19,20]. One study reported that nearly one-half of girls with premature pubarche will develop PCOS [21], although another reported a lower risk of 15 to 20 percent [22]. (See "Premature adrenarche").

DIFFERENTIAL DIAGNOSIS — Although PCOS accounts for more than 90 percent of androgen excess in adolescent females, there are a number of conditions other than PCOS that present with androgen excess. Often, these diseases have similar clinical findings and are difficult to distinguish from PCOS or other causes of hyperandrogenism. The evaluation for hyperandrogenism utilizes findings on pelvic ultrasonography and specific endocrine tests (such as prolactin, insulin growth factor-I, cortisol, 17-hydroxyprogesterone levels, and dexamethasone suppression) to differentiate among the many causes of hyperandrogenism. (See "Evaluation for hyperandrogenism" below).

The conditions that share many presenting features with PCOS are discussed in the following sections (show table 1).

Congenital adrenal hyperplasia — Congenital adrenal hyperplasia (CAH) arises from an autosomal recessive deficiency in the activity of any one of the adrenocortical enzyme steps necessary for the biosynthesis of corticosteroid hormones in the adrenal gland. Nonclassic ("late-onset") CAH is the second most common cause of androgen excess that presents in adolescence; it accounts for approximately 5 percent of hyperandrogenism [23]. Nonclassic CAH usually results from a mild deficiency of 21-hydroxylase and lacks the genital ambiguity of classic CAH. Affected patients may present with premature pubarche, adolescent- or adult-onset hirsutism, and/or symptoms of anovulation. Females with nonclassic CAH may have polycystic ovaries and elevated serum LH levels. They respond to glucocorticoid therapy [24]. (See "Overview of congenital adrenal hyperplasia due to CYP21A2 (21-hydroxylase) deficiency", section on Clinical presentations).

In addition, mild deficiencies of 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) and 11-beta-hydroxylase are types of nonclassic CAH that on rare occasions have presented in adolescence with symptoms of hyperandrogenism. (See "Uncommon causes of congenital adrenal hyperplasia").

Classic 21-hydroxylase deficiency CAH is the most well-known form of CAH. It typically presents with virilization of affected females, and often presents as a salt-losing crisis in the newborn period in either sex. If poorly controlled by glucocorticoid therapy, the combination of virilization and progestin excess causes ovarian dysfunction by inhibiting luteinizing hormone (LH) pulsatility [25,26]. The direct effects of extreme extraovarian androgen excess on the ovaries cause the induction of polycystic ovaries [24].

Both nonclassic and classic CAH often are associated with nonclassic PCOS (hyperandrogenism without ultrasonographic evidence of ovarian dysfunction), which causes persistent menstrual irregularity and insulin resistance in patients who are well controlled on glucocorticoid therapy [24,27,28]. This secondary PCOS may result from in-utero virilization [29]. In rare cases of CAH, adrenal rests of the ovaries seem responsible for FOH [24].

Ovarian steroidogenic blocks — Steroidogenic blocks (such as 3-beta-hydroxysteroid dehydrogenase [30], 17-beta-hydroxysteroid dehydrogenase [31], or aromatase deficiency [32]) in ovarian steroid synthetic pathways can cause hyperandrogenism in association with polycystic ovaries and elevated LH levels (show figure 3).

Other adrenal disorders — Dexamethasone-resistant forms of hyperandrogenism include Cushing's syndrome [33], cortisol resistance [34], and apparent cortisone reductase deficiency [35]. These are not commonly found in adolescents. Clinical features of Cushing's syndrome include central obesity, dorsal fat pad, hypertension, easy bruising, striae, and proximal muscle weakness. These findings may occur in the pseudo-Cushing's syndrome of PCOS insulin resistance. Although not a main feature, polycystic ovaries can sometimes occur in Cushing's syndrome [33]. (See "Manifestations of insulin resistance" above, and see "Clinical manifestations of Cushing's syndrome").

Hyperprolactinemia — In our experience, excess prolactin is a distant second cause of hyperandrogenism to CAH [36]. About 40 percent of hyperprolactinemic women have androgen excess. The combination of hirsutism, galactorrhea, and amenorrhea comprises the Forbes-Albright syndrome. Some patients also will have polycystic ovaries on ultrasound [37], and only half of hyperprolactinemic will have galactorrhea. Excess prolactin may be caused by a pituitary adenoma, and such patients can present with headaches or galactorrhea, in addition to menstrual irregularities. (See "Clinical manifestations and diagnosis of hyperprolactinemia").

Acromegaly — Acromegaly resulting from excess of the insulin growth factor-I (IGF-I) also is associated with PCOS, and its presentation can be insidious [38]. Acromegaly needs to be distinguished from pseudo-acromegaly [15]. (See "Clinical manifestations of acromegaly").

Insulin-resistance disorders — All extreme states of insulin-resistant hyperinsulinemia, such as hereditary cases because of insulin-receptor mutations, are accompanied by PCOS [36]. In addition, more modest forms of insulin resistance also are associated with PCOS including type 1 [39-41] and type 2 diabetes mellitus [42,43].

Virilizing tumors — Although virilizing tumor is a rare cause of hyperandrogenism, they are serious, as more than half are malignant [2]. Virilization is suggested by rapid onset of hirsutism, voice change, onset of clitoromegaly without genital ambiguity, Cushingoid changes, and/or abdominal or pelvic masses. A substantial minority of these tumors are indolent in onset and mimic PCOS in their presentation. Virilization during pregnancy may be because of androgen hypersecretion by chorionic gonadotropin-dependent ovarian cysts (either luteoma or hyperreaction luteinalis) [44]. Acanthosis nigricans may occur with virilizing tumors, though it is an uncommon feature and more suggestive of PCOS [45,46].

Thyroid dysfunction — Thyroid dysfunction interferes with sex hormone metabolism and causes menstrual irregularity. Hypothyroidism causes menstrual irregularity, cystic ovarian changes, and low sex hormone binding globulin.

Drugs — Anabolic steroids cause virilization in women and present with features similar to those of virilizing tumors. Valproic acid directly augments the transcription of the steroidogenic gene cytochrome P450c17. This results in excess androgen production [47] (show figure 3). (See "Steroid hormone metabolism in polycystic ovary syndrome", section on Control of androgen production).

Other causes — Other rare conditions that are included in the differential diagnosis of PCOS include:

Hermaphroditism — Rarely, phenotypic females have mixed ovarian and testicular tissue (either ovotestis, or ovary and testis). The development of the internal and external genitalia in these children can be quite variable depending upon androgen production and exposure. (See "Evaluation of the infant with ambiguous genitalia").
Portohepatic shunting — Impaired steroid metabolism can occur as a complication of portal hypertension or portosystemic shunting [48,49].
Idiopathic — Approximately 8 percent of hyperandrogenic patients have no ascertained cause despite thorough testing; such patients are said to have idiopathic hyperandrogenemia. Few of these patients have menstrual abnormalities. Obesity may be responsible for some of these cases because adipose tissue has the capacity to form testosterone from androstenedione [50]. Obesity may mimic PCOS by causing amenorrhea, acanthosis nigricans, and hyperandrogenemia, all of which correct with weight loss [3,39]. Other idiopathic cases may be caused by hereditary defects in peripheral metabolism of steroids.

DIAGNOSTIC CRITERIA — PCOS is characterized by the following clinical features:

Hyperandrogenism (eg, hirsutism, severe acne, and/or pattern alopecia)
Menstrual irregularity (eg, oligo- or amenorrhea, or irregular bleeding)
Polycystic ovaries
Central adiposity
There is a spectrum of disease in individual patients such that no clear consensus exists regarding the diagnostic criteria for PCOS. Two major diagnostic criteria have been proposed (show table 2) [51,52]. The NIH criteria require the presence of evidence of hyperandrogenism and menstrual irregularity (eg, symptoms of anovulation) that are not explained by another disorder, although the Rotterdam criteria clarified that oligoovulation is evidence of anovulation. The Rotterdam criteria added a third finding, the presence of polycystic ovary, as an alternative to the two NIH criteria. However, it is controversial whether a patient who has only menstrual irregularity and polycystic ovaries has PCOS [53]. (See "Definition, pathogenesis, and etiology of polycystic ovary syndrome in adolescents").

However, these diagnostic criteria do not include the whole spectrum of disease in patients with PCOS, such as the hyperandrogenic patient with central obesity who lacks clinical evidence of ovarian dysfunction. (See "Definition, pathogenesis, and etiology of polycystic ovary syndrome in adolescents", section on Definition, adults).

Furthermore, neither of these criteria fully addresses some of the unique issues in diagnosing PCOS in adolescents. As an example, even in girls without PCOS, anovulation occurs in approximately one-half of menstrual cycles in the first two years after menarche [5]. The multifollicular ovary of the normal adolescent also may be confused with the polycystic ovary of an adult woman with PCOS. In addition, fewer adolescents than adult women have polycystic ovaries noted on transabdominal ultrasound. (See "Definition, pathogenesis, and etiology of polycystic ovary syndrome in adolescents", section on Definition, adolescents and see "Polycystic ovaries" above).

As a result, we place considerable importance on the presence of hyperandrogenism in adolescents, and define PCOS as chronic, unexplained, biochemically confirmed hyperandrogenemia of ovarian or adrenal origin.

INDICATIONS FOR EVALUATION — Evaluation for PCOS is recommended in the following clinical scenarios:

Girls with a sole finding of moderate or severe hirsutism, or a hirsutism equivalent, including treatment-resistant acne vulgaris, seborrhea, or pattern alopecia.
Girls with mild hirsutism or obesity with any other feature of PCOS (eg, menstrual abnormality).
Adolescent girls with menstrual irregularity that persists more than two years or who have severe dysfunctional uterine bleeding.
Adolescent girls with intractable obesity whether or not hirsutism, hirsutism equivalents, or menstrual irregularity are present.
DIAGNOSTIC APPROACH — The evaluation for PCOS includes the following:

Androgen testing — Normal androgen levels effectively rule out the diagnosis of PCOS in adolescents. However, the ovarian hyperandrogenism of PCOS may not become demonstrable until a few years after menarche [9]. Thus, the diagnosis of PCOS should not be dismissed until a follow-up evaluation demonstrates that androgen levels remain persistently normal after the onset of menarche. Patients with elevated androgen levels require further evaluation.
Evaluation for hyperandrogenism — This includes ultrasonography and several specific endocrine tests to determine the underlying cause of hyperandrogenism. This evaluation will exclude the vast majority of disorders that mimic PCOS, addresses the Rotterdam third criterion (evaluating for the presence of a polycystic ovary) [52], and also meets the American College of Obstetrics and Gynecology guidelines for the diagnosis of PCOS [54]. Dexamethasone androgen suppression test is reserved for patients in whom the initial evaluation fails to identify a cause of androgen excess.
The American Association of Clinical Endocrinologists' guidelines recommends a comprehensive evaluation including dexamethasone suppression testing and cosyntropin testing, which determine the source of androgen and includes diagnoses of rare congenital disorders [55].

Evaluation after the diagnosis of PCOS — Girls diagnosed with PCOS should have additional evaluations to look for glucose intolerance and dyslipidemia.
Androgen testing — Although hyperandrogenism can be based upon clinical or biochemical finding(s), we agree with the guidelines from the American College of Obstetrics and Gynecology and the American Association of Clinical Endocrinologists that recommend biochemical documentation of androgen excess (elevated plasma total or free testosterone levels) [54,55]. Androgen determinations are most accurately performed by a specialty laboratory [2].

An elevation in free testosterone is the most sensitive test to establish the presence of hyperandrogenemia [2,56]. This is because elevated insulin levels (a frequent concomitant of PCOS) and elevated androgen levels both act to inhibit hepatic production of sex hormone-binding globulin (SHBG). As a result, total testosterone levels may be normal despite excess free testosterone.

Nevertheless, it is reasonable to begin the evaluation with a total testosterone determination if a free testosterone test in a specialty laboratory is not readily available. A high level is an accurate indicator of hyperandrogenism. Patients who have marginally elevated levels of testosterone (within 20 ng/dL or 0.69 nmol/L of the upper limit of normal) should have verification of hyperandrogenism with free testosterone levels.

The normal upper limit for plasma total testosterone in women is 70 to 90 ng/dL (2.4 to 3.1 nmol/L). This wide range of the normal upper limits may be related to systematic differences among assays, and/or the inclusion of patients with unrecognized androgen excess within the general population used to determine normative total testosterone values. Most patients with PCOS have serum testosterone concentrations below 150 ng/dL (5.2 nmol/L). A total testosterone >200 ng/dL (6.9 nmol/L) increases the likelihood of a virilizing neoplasm.

There is no uniform laboratory assay for free testosterone, so normative values are based upon the selected assay. The most reliable free testosterone assays compute free testosterone from direct measurements of total testosterone and SHBG. Assays that directly measure free testosterone are not reliable.

Patients who have clinical features consistent with PCOS but have an initial normal testosterone should have repeat testing. It may be reasonable to consult with a specialist at this point, if available, as confounding factors such as the timing of the sample and SHGB levels may have influenced the results.

Dehydroepiandrosterone sulfate (DHEAS) is a marker for adrenal hyperandrogenism. Measurement is not necessary in the initial evaluation of PCOS in most girls. The major utility of measuring DHEAS levels is to rapidly identify an unusual virilizing adrenal disorder, particularly adrenal tumor, and to a lesser extent nonclassic CAH. Girls with a virilizing tumor usually present with a rapid onset of virilizing features and DHEAS levels are often markedly elevated (>700 mcg/dL, 13.6 mmol/L) if the tumor is of adrenal origin. However, a substantial minority are indolent in onset and mimic PCOS in their presentation. (See "Virilizing tumors" above).

Evaluation for hyperandrogenism — The goal of the endocrinologic evaluation of a hyperandrogenic female is to identify the underlying cause of androgen excess. The diagnosis of PCOS is made when other hyperandrogenic disorders are excluded (show table 3). (See "Differential diagnosis" above).

We suggest an algorithm that utilizes ultrasonography as an initial test primarily to screen for tumors and ovarian pathology not related to PCOS (show algorithm 1). Depending on the results, further endocrinologic evaluation includes measurement of prolactin, insulin growth factor-I (IGF-I), thyroid function, 17-hydroxyprogesterone, and cortisol levels. All of these endocrine studies will be normal in patients with PCOS. Abnormal results suggest an alternate etiology for hyperandrogenism.

Ultrasonography — In girls with laboratory-confirmed testosterone elevation, we recommend obtaining ultrasonography primarily to exclude the rare but serious adrenal or ovarian tumor (show algorithm 1). In addition, other ovarian pathology including hermaphroditism and the functional hyperandrogenism of pregnancy can be detected by ultrasonography.

Ultrasonography also can identify ovarian changes consistent with PCOS (show radiograph 1).

Ovarian enlargement, which is an indicator of excessive ovarian stroma, is the most specific ultrasonographic finding for a polycystic ovary in adolescents. A polycystic ovary in adolescents is similar in size to that of adults, with increased volume defined as >10.8 cubic mL [4]. An alternate measure of increased volume is a maximal area >5.5 cm2 [57]. (See "Diagnosis of polycystic ovary syndrome in adults").
Multiple follicles (>10 per maximum plane or >12 per ovary) are a feature of polycystic ovaries. However, in the absence of ovarian enlargement, up to 10 follicles is defined as a multifollicular ovary and the distinction from polycystic ovary is problematic. This is particularly true in adolescents because multifollicular ovaries are seen normally in this age group as well as other anovulatory states [58].
The transabdominal ultrasonographic approach that is standard and the appropriate study in virginal adolescents probably underestimates the prevalence of polycystic ovaries in comparison to the transvaginal approach used in adult women [59]. The advantage of the transabdominal approach is that a screening for an adrenal mass is facilitated. (See "Diagnosis of polycystic ovary syndrome in adults").
Girls who have an ultrasound that shows an ovarian tumor or other explanation for hyperandrogenism should be referred for treatment of the underlying disorder. Hyperandrogenic girls who have a normal ultrasound or ultrasound findings consistent with PCOS need further endocrine evaluation.

Endocrine studies — The following endocrine studies are performed in girls with laboratory-confirmed hyperandrogenism regardless of whether the ultrasound is normal or consistent with PCOS. In patients with PCOS, all these studies will be normal. An abnormal result suggests another cause of hyperandrogenism.

Prolactin — Serum prolactin values between 20 and 200 ng/mL (20 to 200 mcg/L SI units) can be found in patients with any cause of hyperprolactinemia. Serum prolactin values above 200 ng/mL usually indicate the presence of a lactotroph adenoma. (See "Clinical manifestations and diagnosis of hyperprolactinemia").
Insulin-like growth factor-I — Serum IGF-I concentrations are elevated in virtually all patients with acromegaly and provide excellent discrimination from normal individuals. They are indicated in patients who undergo acral overgrowth, rapid statural growth, or who have symptoms suggestive of a pituitary tumor. (See "Diagnosis of acromegaly").
Random serum cortisol — A random cortisol concentration of <10 mcg/dL (276 nmol/L) provides evidence against endogenous Cushing's syndrome. (See "Establishing the diagnosis of Cushing's syndrome").
Thyroid function tests — Measurements of serum TSH and free T4 (or serum total T4 with some assessment of serum binding proteins) are adequate to rule out hypothyroidism. (See "Acquired hypothyroidism in childhood and adolescence").
Early-morning 17-hydroxyprogesterone — The sample should be obtained before 8 AM, and either during the follicular phase of the cycle or while the patient is anovulatory. A value of >400 ng/dL (12 nmol/L) is suggestive of congenital adrenal hyperplasia (CAH) and a value >1200 ng/dL (36 nmol/L) virtually assures this diagnosis. Virilizing tumors, which are rare, also may cause very high levels [60]. (See "Overview of congenital adrenal hyperplasia due to CYP21A2 (21-hydroxylase) deficiency").
Girls with an abnormality of one of these tests for disorders that mimic PCOS should be managed appropriately.

It is most likely the patient has PCOS if all of these screening tests are normal and pregnancy is excluded as a cause of amenorrhea. The evaluation to this point both assesses for the Rotterdam criterion for the presence of a polycystic ovary [52] and fulfills the American College of Obstetrics and Gynecology guidelines for the diagnosis of PCOS [9] if the patient has anovulatory symptoms or a polycystic ovary. However, this exclusionary approach will miss a few patients with rare disorders. Therefore, these patients must be followed closely to be sure they respond to therapy as expected.

More thorough endocrine testing, as recommended by the American Association of Clinical Endocrinologists [55], will detect the small fraction of patients who have rare disorders that mimic PCOS and is indicated in those patients with hyperandrogenemia detected in the workup of hirsutism, acne, or obesity who do not have menstrual disturbance or a polycystic ovary, as is often the case in a pediatric or medical practice. The cost-effectiveness of this approach is unknown.

Although the specific approach differs among endocrinologists, we augment the initial evaluation by starting with the dexamethasone suppression test to distinguish an ACTH-dependent adrenal source of androgen excess from other sources of androgen (show algorithm 2) [3]. The responses of androgens (testosterone, DHEAS, and 17-hydroxyporgesterone) and cortisol levels to dexamethasone suppression establish the underlying cause of hyperandrogenism.

If both androgen excess and cortisol are not suppressed, Cushing's syndrome, adrenal tumors, and other adrenal disorders must be considered. If the levels of androgen suggest an adrenal tumor, imaging, such as computed tomography, is indicated.
If testosterone excess is not suppressed but cortisol and DHEAS are suppressed, the diagnosis of PCOS is virtually assured.
If androgen excess is suppressed, then further evaluation with a cosyntropin (ACTH) test for CAH is indicated.
(See "Dexamethasone suppression tests" and see "Evaluation of the response to ACTH in adrenal insufficiency").

Additional evaluation — Once a diagnosis of PCOS has been established, identifying abnormal glucose tolerance or dyslipidemia is important because PCOS is a risk factor for the early development of type 2 diabetes mellitus, metabolic syndrome, and their associated cardiovascular risk sequelae.

We agree with the recommendation of the American Association of Clinical Endocrinologists and American College of Obstetrics and Gynecology that a baseline lipid panel plus an oral glucose tolerance test (OGTT) be obtained, as a fasting glucose concentration is poorly predictive of the two-hour level in PCOS [54,55]. A two-hour blood glucose 140 mg/dL (7.77 mmol/L) is presumptive of insulin resistance based upon the American Diabetes Association (ADA) guidelines. An abnormal OGTT has important therapeutic implications.

When an OGTT is not practical, a fasting glucose along with a hemoglobin A1C can be obtained. If either one is abnormal, an OGTT should be performed to distinguish between impaired glucose tolerance and diabetes. (See "Treatment of polycystic ovary syndrome in adolescents").

Glucose tolerance should be monitored regularly because the two-hour blood glucose deteriorates at an average of 9 mg/dL (0.5 mmol/L) per year [61]. In addition, approximately one-third of PCOS patients have a primary relative with type 2 diabetes. Thus, it may be reasonable to suggest the parents be screened for impaired glucose tolerance.

INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. (See "Patient information: Treatment of polycystic ovary syndrome"). We encourage you to print or e-mail this topic review, or to refer patients to our public web site, www.patients.uptodate.com, which includes this and other topics.

SUMMARY

Recognizing and treating PCOS in adolescents are important beyond management of the presenting symptoms because PCOS increases the risk of developing endometrial hyperplasia and carcinoma, type 2 diabetes mellitus, metabolic syndrome, infertility, and possibly cardiovascular disease.
PCOS is characterized by hyperandrogenism (eg, hirsutism, severe acne, pattern alopecia), and/or menstrual irregularity (eg, oligo- or amenorrhea, irregular bleeding), or polycystic ovaries. However, standard diagnostic criteria in women are more difficult to apply to adolescents who are normally oligo-ovulatory and are less likely to have polycystic ovaries. As a result, we define PCOS as chronic, confirmed hyperandrogenemia of ovarian or adrenal origin that is otherwise unexplained. (See "Diagnostic criteria" above).
PCOS should be considered in any adolescent girl with hirsutism or hirsutism equivalents, menstrual irregularity, and/or obesity. These patients should be tested for androgen excess. (See "Androgen testing" above and see "Indications for evaluation" above).
Once androgen excess has been confirmed by laboratory testing, other hyperandrogenic disorders are excluded by the combination of ultrasonography and endocrine testing (show algorithm 1 and show table 3). (See "Evaluation for hyperandrogenism" above and see "Differential diagnosis" above).
Once a diagnosis of PCOS has been established, identifying and monitoring abnormal glucose tolerance or dyslipidemia are important because PCOS is a risk factor for the early development of type 2 diabetes mellitus and metabolic syndrome, and their associated morbidity. (See "Additional evaluation" above).

INTRODUCTION — Hirsutism is the development of androgen-dependent terminal body hair in a woman. The most common causes of hirsutism are the polycystic ovary syndrome (PCOS) and idiopathic hirsutism.

Using the Rotterdam criteria, a woman with hirsutism, regular ovulatory cycles and ultrasound evidence of a multi-follicular ovary by transvaginal sonography would be diagnosed as having PCOS. Prior to the development of the Rotterdam criteria, this woman might have been diagnosed with idiopathic hirsutism. (See "Pelvic ultrasonography" below and see "Diagnosis of polycystic ovary syndrome in adults").
Idiopathic hirsutism is defined as hirsutism with no other clinical abnormalities, particularly no menstrual irregularity; and using the Rotterdam criteria, no evidence of a multifollicular ovary. It may well be a mild variant of PCOS.
Less common causes of hirsutism include hyperprolactinemia, drugs, congenital adrenal hyperplasia, and ovarian and adrenal tumors (show table 1). (See "Pathogenesis and causes of hirsutism" and see "Clinical manifestations of polycystic ovary syndrome in adults").

The evaluation and laboratory testing of hirsutism will be discussed here, while its pathogenesis, causes and treatment are discussed elsewhere. (See "Pathogenesis and causes of hirsutism" and see "Treatment of hirsutism")

BASIC APPROACH — Given that most women with hirsutism have idiopathic hirsutism or PCOS, the problem is how best to identify the small number of women who have other causes for their hirsutism. The basic approach to the differential diagnosis should be:

Documentation of the degree of androgen excess
Exclusion of the serious but rare causes of hirsutism such as ovarian and adrenal androgen-secreting tumors
There are several clinical findings that suggest one of the rare and more serious causes of hirsutism:

Abrupt onset, short duration (typically less than 1 year), or progressive worsening of hirsutism.
Onset in the third decade of life or later, rather than near puberty.
Symptoms or signs of virilization, including frontal balding, acne, clitoromegaly, increased muscle mass, or deepening of voice. More severe hirsutism and virilization are typically seen in ovarian hyperthecosis. (See "Ovarian hyperthecosis").
Moderately elevated (or higher) serum androgen concentrations, eg, serum testosterone values above 150 ng/dL (5.2 nmol/L) [1]; serum free testosterone values above 2 ng/dL (0.07 nmol/L) [2]; and serum dehydroepiandrosterone sulfate (DHEA-S) values above 700 mcg/dL (13.6 µmol/L) in young women raise the possibility of an androgen-secreting tumor [3].
HISTORY AND PHYSICAL EXAMINATION — Important clues to the severity of androgen excess and the presence of specific causes of the excess can be obtained by the history and physical examination and appropriate laboratory testing [4,5].

History — The history should include the following information:

Menstrual history — The menstrual history should include age at menarche, regularity of menstrual cycles, pregnancies, oral contraceptive use (why, when, for how long, which pills, response) and presence of symptoms of ovulation or of premenstrual symptoms (ovulatory pain, premenstrual discomfort, breast tenderness). Women with consistently regular cycles and symptoms of ovulation are unlikely to have severe hyperandrogenemia. A woman who has irregular cycles should be evaluated for hyperprolactinemia. Prior oral contraceptive use may have masked or delayed the recognition of menstrual dysfunction or hyperandrogenic symptoms.
Time course of symptoms — The age at onset, the rate of progression, and any change with any treatment or with fluctuations in weight should be determined. As noted above, progressive worsening of hirsutism, a later age of onset, or rapid rate of progression suggest the possibility of ovarian or adrenal tumor, but could be caused by responses to previous treatments or changes in weight.
Weight history — Obese women have increased androgen production and clearance rates [6], each of which aggravate hirsutism and increase the likelihood of menstrual irregularity, especially in those with PCOS.
Medication history — Drugs that cause hirsutism or have other androgenic effects include danazol (which was often given for endometriosis) and oral contraceptives that contain androgenic progestins such as levonorgestrel.
Family history — Hirsutism, acne, menstrual irregularity, infertility, early cardiovascular disease, and obesity are all potential indicators of a familial tendency towards the PCOS. A family history of infertility and/or hirsutism may also indicate disorders such as non-classic congenital adrenal hyperplasia, a disorder particularly common in Ashkenazi Jewish women [7]. (See "Overview of congenital adrenal hyperplasia due to CYP21A2 (21-hydroxylase) deficiency").
Physical examination — The physical examination provides information about the extent of hirsutism and sometimes about its cause (show figure 1). In particular, does the woman have hirsutism as opposed to hypertrichosis? Hirsutism is the presence of an increase in androgen-dependent terminal hair on the lip, chin, chest, abdomen, and back, areas where there are few or no hairs in normal women.

Hypertrichosis is the term used to describe the excessive growth of androgen-independent hair which is vellus, prominent in non-sexual areas, and most commonly familial or caused by systemic disorders (hypothyroidism, anorexia nervosa, malnutrition, porphyria, and dermatomyositis) or medications (phenytoin, penicillamine, diazoxide, minoxidil, or cyclosporine).

Ferriman-Gallwey score — A simple and commonly used method to grade hair growth makes use of the modified scale of Ferriman and Gallwey, which was derived from a cohort of Caucasian women. Using this method, nine androgen-sensitive sites are graded from 0 to 4 (show figure 1) [8,9]. Approximately 95 percent of women will have a score below 8; however, the majority of women with a score above 3 consider themselves to be hirsute [10]. Thus, it is normal for most women to have at least some hair growth in androgen sensitive sites. Scores above 8 suggest an excess of androgen-mediated hair growth which should be confirmed by hormonal evaluation (see below). The expression of hair growth varies between racial/ethnic groups and should be noted in the clinical assessment. As an example, Asian women are less likely to manifest hirsutism resulting from androgen excess than are Caucasian or African-American women. In these cases, additional cutaneous evidence of androgen excess should be sought, including acne and hair thinning and/or loss.

Although intraobserver agreement may be reasonable when using the modified Ferriman-Galwey score [11], interobserver reproducibility appears to be poor [12].

Body habitus — Height, weight, and a calculation of body mass index (BMI) should be obtained. Many women with PCOS are obese (BMI 30 kg/m2). In addition, the pattern of body fat distribution (truncal obesity, a buffalo hump, and supraclavicular fat) may suggest the presence of Cushing's syndrome. (See "Clinical manifestations of Cushing's syndrome").

Skin — Acne, seborrhea, temporal balding (which are additional signs of androgen excess), acanthosis nigricans, striae, thin skin, or bruising should be sought. The last three findings suggest the possible presence of Cushing's syndrome, whereas acanthosis nigricans may suggest insulin resistance.

Signs of virilization — In addition to acne, deepening of the voice, frontal (or crown) balding, increased muscle mass, and clitoromegaly indicate the presence of moderate androgen excess. Although there is significant variability in clitoral size in normal women [13], in one study, mean glans clitoral length and width were 5.1 ± 1.4 and 3.4 ± 1.0 mm, respectively [14]. However, clitoral enlargement is typically determined on the basis of clitoral length or the clitoral index (length times width): length >10 mm or an index >35 mm2 is considered above normal [15].

Galactorrhea — The presence of any breast discharge, spontaneous or expressible, is suggestive of hyperprolactinemia and warrants measurement of serum prolactin even if the woman's menstrual cycles are regular.
Abdominal and pelvic examination — These examinations may reveal mass lesions that could indicate the presence of an androgen-secreting tumor.
LABORATORY TESTING — Most physicians recommend some laboratory evaluation for many but not all women with hirsutism [16]. The tests that provide the most useful information are measurements of serum testosterone, prolactin, and DHEA-S, although other tests may be indicated in selected patients. DHEA-S is almost entirely derived from the adrenal gland whereas testosterone, in hirsute women, is mostly secreted by the ovary.

Serum androgens — The principal circulating steroids involved in the etiology of hirsutism are androstenedione (AD), dehydroepiandrosterone (DHEA) and its sulfated form (DHEAS), and testosterone (T). In women, the ovaries and adrenal glands normally contribute approximately equally to testosterone production. Further, approximately half of the total testosterone originates from direct glandular secretion, while the remaining half is derived from the peripheral conversion of androstenedione and dehydroepiandrosterone. This conversion occurs in the liver, adipose tissue, and skin, which contain enzymes that allow for the further processing of steroids originating from the adrenal and ovary.

The primary reason to measure serum androgen concentrations is to exclude the serious but rare causes of hirsutism such as ovarian and adrenal androgen-secreting tumors. The serum testosterone concentration, measured as either total or free testosterone, provides the best overall estimate of androgen production in hirsute women, and therefore is the single best test for evaluating them. Serum total testosterone measurements are more widely available, and better standardized than are those of free testosterone. They are sufficient to exclude androgen-secreting tumors in most women; specifically, values below 150 ng/dL (5.2 nmol/L) exclude ovarian or adrenal tumors [1,2,17,18]. (See "Sex cord-stromal tumors of the ovary", section on Sertoli-Leydig cell tumor). These values also tend to exclude ovarian hyperthecosis. (See "Ovarian hyperthecosis"). Conversely, most women with PCOS have serum testosterone concentrations below 150 ng/dL (5.2 nmol/L), and the values are sometimes normal; women with idiopathic hirsutism are even more likely to have normal values.

In all women with androgen excess, serum free testosterone concentrations are disproportionately higher than serum total testosterone concentrations, because of a reduction in the serum sex hormone-binding globulin concentration. The reduction is due to reduced hepatic production of this protein due to androgen excess and, in women with PCOS, to hyperinsulinemia [19]. The difference is most evident in women with idiopathic hirsutism, in whom serum free testosterone may be high but serum total testosterone is normal.

Therefore, measurements of serum free testosterone are a more sensitive indicator of androgen excess. However, many assays for free testosterone are inaccurate [20]. Free testosterone by equilibrium dialysis or calculated using total testosterone and SHBG results are the preferred methods. However, they are not routinely indicated, because serum total testosterone measurements readily identify those women who need further evaluation for a possible androgen-secreting tumor [20].

Serum DHEA-s should also be drawn; concentrations >700 mcg/dL (13.6 µmol/L) raise suspicion for an adrenal androgen-secreting tumor.

Serum prolactin — Serum prolactin should be measured in women with hirsutism and irregular menstrual cycles to rule our hyperprolactinemia. However, hirsutism due to hyperprolactinemia is thought to be quite rare. Thus, a moderately elevated value should be followed by imaging of the hypothalamic-pituitary region. (See "Causes of hyperprolactinemia").

There are a number of other tests that may be performed in the evaluation of selected women with hirsutism:

Serum luteinizing hormone (LH) — Women with PCOS tend to have elevated serum LH concentrations and normal or low serum FSH concentrations. In the past, the diagnosis of PCOS was often based upon the finding of an elevated ratio of LH to FSH in serum. However, a high ratio is not required for the diagnosis, because LH secretion is pulsatile and many women who have PCOS have normal serum LH concentrations [21]. (See "Clinical manifestations of polycystic ovary syndrome in adults").

Pelvic ultrasonography — High-resolution pelvic ultrasonography with a transvaginal probe can identify ovarian follicles and cysts as small as 3 to 5 mm in diameter. It is therefore a safe and effective way to look for a polycystic ovary and to screen for ovarian androgen-secreting tumors. Suspicious findings include large cysts, solid masses, and complex cysts that do not resolve spontaneously in two to four weeks. However, the sensitivity and specificity of ultrasonography for the diagnosis of ovarian tumors in hyperandrogenic women has not been determined. Small hilus-cell tumors of the ovary that produce large amounts of testosterone may not be seen by ultrasonography or even at the time of surgery.

Pelvic ultrasonography can also be used to identify polycystic ovaries. The ultrasound criteria for polycystic ovaries (PCO) have evolved since the first description in 1986. The current criteria considered to have sufficient specificity and sensitivity to define PCO are the presence of 12 or more follicles in each ovary measuring 2 to 9 mm in diameter and/or increased ovarian volume (>10 mL; calculated using the formula 0.5 x length x width x thickness). It was suggested that follicle distribution and an increase in stromal echogenicity and volume be eliminated as diagnostic criteria.

The correlation between polycystic ovaries, as detected by ultrasonography, and PCOS is only fair. In one study, for example, 83 percent of 173 women with hirsutism had polycystic ovaries on ultrasonography [22], as did 23 percent of 158 regularly menstruating women in another study [23]. Furthermore, women with non-ovarian causes of hirsutism, such as congenital adrenal hyperplasia and adrenal tumors, may have polycystic-appearing ovaries. (See "Diagnosis of polycystic ovary syndrome in adults").

In summary, pelvic ultrasonography is indicated in patients with an elevated serum androgen concentration when an ovarian androgen-secreting tumor is suspected (total testosterone >150 ng/dL). It may also be indicated to exclude endometrial hyperplasia, which is common in PCOS due to unopposed estrogenic activity. (See "Clinical manifestations of polycystic ovary syndrome in adults").

17-OH progesterone — Late-onset CYP21A2 deficiency is characterized by symptoms and signs of androgen excess in girls at the time of puberty or soon thereafter. These patients have acne, hirsutism and menstrual irregularity that are indistinguishable from the polycystic ovary syndrome.

Testing for CYP21A2 deficiency should be considered in women with an early onset of hirsutism (including those with premature adrenarche), hyperkalemia, a family history of congenital adrenal hyperplasia, or a strong desire to know a specific etiologic diagnosis. In addition, testing should be considered for women who are Hispanic, Yugoslav, or Eastern European Jewish, because the prevalence of the disorder is higher in these women than in other ethnic groups [7]. (See "Overview of congenital adrenal hyperplasia due to CYP21A2 (21-hydroxylase) deficiency", section on Prevalence).

Basal serum 17-hydroxyprogesterone concentrations (during the follicular phase of the menstrual cycle) may be only slightly high, especially late in the day, but are always greater than 200 ng/dL (6 nmol/L). A morning value greater than 200 ng/dL in the early follicular phase strongly suggests the diagnosis, which may be confirmed by a high dose (250 mcg) ACTH stimulation test. The response to ACTH is exaggerated, and most patients have values exceeding 1500 ng/dL (43 nmol/L) after ACTH stimulation. [7,24,25].

If performed without adrenal stimulation, the blood sample must be obtained in the early morning to take advantage of the fact that endogenous ACTH levels are highest at that time as a result of the diurnal variation in its secretion. Measurement after ACTH is given is slightly more cumbersome, but the results obtained in this manner are highly reproducible and can be compared to published nomograms [7].
(See "Overview of congenital adrenal hyperplasia due to CYP21A2 (21-hydroxylase) deficiency", section on Laboratory findings).

Anti-androgen therapy, such as oral contraceptives and/or spironolactone, can be as effective as glucocorticoid therapy in ameliorating hirsutism in women with late-onset congenital adrenal hyperplasia. As a result, many physicians do not think it important to make this diagnosis in hirsute women; others argue that is worthwhile because of the need for genetic counseling if the woman is likely to conceive with a partner who also has a high risk for carrying the disease. (See "Overview of congenital adrenal hyperplasia due to CYP21A2 (21-hydroxylase) deficiency" and see "Treatment of hirsutism").

Testing for Cushing's syndrome — Some hirsute women have symptoms and signs of cortisol excess, such as obesity, hypertension, striae, that suggest the presence of Cushing's syndrome. Screening for this disorder is indicated in such patients. This can be done by measuring 24-hour urinary excretion of cortisol (and creatinine) or by performing an overnight dexamethasone suppression test. (See "Establishing the diagnosis of Cushing's syndrome").

Abdominal CT or MRI — Adrenal imaging is indicated to look for an adrenal mass if the woman has a markedly elevated serum DHEA-S concentration or other evidence of excess adrenal steroid production. Radiologic testing is otherwise not indicated, and may be misleading, because nonfunctioning adrenal masses are common. (See "The adrenal incidentaloma").

Laparoscopy or laparotomy — One of these procedures should be considered in a hirsute woman who has menstrual abnormalities, a serum testosterone concentration above 200 ng/dL (6.9 nmol/L), no evidence of an adrenal tumor, and a negative pelvic ultrasound. Such a patient may have a small ovarian tumor (especially a hilus-cell tumor) that is too small to be detected by pelvic ultrasonography.

Ovarian and adrenal vein sampling — Organ-specific venous sampling may be used to localize the site of excessive testosterone production in a woman in whom vaginal ultrasonography and abdominal imaging are normal, in anticipation of surgical exploration. However, the need for this procedure is very limited, and its value is highly dependent upon the skill of the radiologist.

Serum 3-alpha-androstanediol glucuronide — This compound is a metabolite of dihydrotestosterone, and therefore its concentration reflects the extent of androgen metabolism in target tissues, including the skin. Serum 3-alpha-androstanediol glucuronide values are usually elevated in hirsute women, even if their serum testosterone concentrations are normal [26]. However, hirsutism itself is an excellent marker of increased androgen metabolism at the skin, so we do not recommend measurement of this metabolite as it adds little useful information.

Dexamethasone suppression testing — Moderately elevated (or higher) serum androgen concentrations, eg, serum testosterone values above 150 ng/dL (5.2 nmol/L) and serum dehydroepiandrosterone sulfate (DHEA-S) values above 700 mcg/dL (13.6 µmol/L) in young women require additional testing to rule out an androgen-secreting tumor [18]. As described above, this may include pelvic ultrasound, adrenal imaging, ovarian and adrenal vein sampling, and laparoscopy, depending upon the clinical presentation.

Dexamethasone suppression testing, which may be indicated in patients with suspected Cushing's syndrome (see "Testing for Cushing's syndrome" above), is also sometimes performed in patients with a suspected adrenal androgen-secreting tumor. In one report, dexamethasone suppression testing (1 mg orally every 8 hours for 5 days with measurements of serum androgens and 17-urinary ketosteroids before and after) was useful for distinguishing adrenal tumors from hirsutism of non-neoplastic origin [18].

Clinical investigation tools

Dexamethasone suppression — In a clinical investigation setting, dexamethasone testing is a useful tool for distinguishing ovarian from adrenal hyperandrogenism [27]. This test is performed by obtaining a blood sample before and after administering dexamethasone, 2.0 mg daily in divided doses by mouth for 4 days. The pattern of response of plasma free testosterone, and DHEAS segregates patients diagnostically. Normal suppression of androgens is most specifically indicated by a reduction of the plasma free testosterone into the normal range as derived from similarly tested normal, non-hirsute women [27].

Dexamethasone suppressibility is considered incomplete ("abnormal") in a peri- or postmenarcheal female if the plasma free testosterone is greater than or equal to 8 pg per mL (27 pmol per liter) and is interpreted to indicate ovarian androgen excess. Subnormal suppressibility of free testosterone is most often due to an ovarian source in which case a diagnosis of functional ovarian hyperandrogenism/polycystic ovary syndrome (PCOS) may be reasonably assigned.

"Normal" adrenal suppression is indicated by a reduction of free testosterone below 8 pg per ml (27 pmol per liter) with reduction of DHEAS to levels below the normal range for adult controls (<70 mcg per dL in our laboratory). In such cases, it may be warranted to exclude nonclassic congenital adrenal hyperplasia, particularly due to 21-hydroxylase deficiency.

GnRH agonist testing — GnRH agonist testing has been utilized as a means of making a specific diagnosis of ovarian hyperandrogenism. In one report, a peak 17-hydroxyprogesterone level of 260 ng per dL (7.8 nmol per liter) or more, after the administration of 100 mcg nafarelin subcutaneously was virtually diagnostic of ovarian hyperandrogenism [27]. A similar peak in 17-hydroxyprogesterone is obtained by the administration of leuprolide at a dose of 10 mcg/kg body weight. However, this test is used primarily for clinical investigation purposes and we do not recommend its use routinely.

RECOMMENDATIONS — Given that most women with hirsutism have idiopathic hirsutism or PCOS, the problem is how best to identify the small number of women who have other causes for their hirsutism. The basic approach to the differential diagnosis should be:

Documentation of the degree of androgen excess
Exclusion of the serious but rare causes of hirsutism such as ovarian and adrenal androgen-secreting tumors.
History — Women should be asked about their menstrual history, time course of the hirsutism, as well as their menstrual, family, weight, and medication history. (See "History" aboveSee "History" above).

Physical examination — The physical exam should focus on the type of hair (hirsutism versus hypertrichosis), height and weight, presence of acne, signs of virilization (deepened voice, balding, clitoromegaly), and ovarian size (or masses) on pelvic exam. (See "Physical examination" aboveSee "Physical examination" above).

Biochemical evaluation — The primary reason to measure serum androgen concentrations is to exclude the serious but rare causes of hirsutism such as ovarian and adrenal androgen-secreting tumors.

We suggest meauring serum total testosterone and DHEA-S if there are any concerns about a possible ovarian or adrenal tumor (recent or rapid onset of hirsutism, onset in the third decade of life or later, rather than near puberty, or symptoms or signs of virilization.) (See "Serum androgens" above).
If the patient also has irregular menses, serum prolactin should be drawn. Other evaluation of irregular menses is the same as for women with oligomenorrhea/amenorrhea without hirsutism. (See "Etiology; diagnosis; and treatment of secondary amenorrhea").
We suggest testing for CYP21A2 deficiency in women with an early onset of hirsutism (including those with premature adrenarche), hyperkalemia, a family history of congenital adrenal hyperplasia, or a strong desire to know a specific etiologic diagnosis. In addition, we suggest testing in women who are Hispanic, Yugoslav, or Eastern European Jewish, because the prevalence of the disorder is higher in these women than in other ethnic groups [7].
A morning value of 17-hydroxyprogesterone greater than 200 ng/dL in the early follicular phase strongly suggests the diagnosis, which may be confirmed by a high dose (250 mcg) ACTH (1-24) (cosyntropyn) stimulation test. The response to ACTH is exaggerated, and most patients have values exceeding 1500 ng/dL (43 nmol/L) after ACTH stimulation.(See "Overview of congenital adrenal hyperplasia due to CYP21A2 (21-hydroxylase) deficiency").

Imaging studies — Further evaluation with imaging studies is indicated in women with marked hyperandrogenemia.

We suggest an adrenal CT scan to look for an adrenal androgen-secreting tumor if serum DHEA-s concentrations are 700 mcg/dL (13.6 µmol/L).
We suggest a transvaginal ultrasound if serum total testosterone concentration is 150 ng/dL (5.2 nmol/L).

Answer 2

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Answer 4

the best thing to do is find out what the cause of the hirsutism is. Get checked to see if she has high levels of androgens. Get checked for PCOS which is the leading cause of hirsutism. If it is PCOS, you can do wonders with a diet that controls insulin resistance. I have PCOS and use of glucophage and a low glycemic diet really helped with excess hair growth

Answer 5

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Answer 6

Sometimes birth control can be used for this. It appears cyproterone acetate is not needed for it to work.
There's a topical product called Estrasorb (estradiol) which might do well.
The pharmacist is always a good resource. He/she has had more drug education than your doctor. He/she has gone to school for a minimum of 6 years to become a pharmacist. I wouldn't trust a pharmacy tech for drug advice, though.
Anyway, have your sister go to her MD for a new script.

Answer 7

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Answer 8

Androgen-excess syndrome has several major features:
*seborrhea (a form of skin inflammation which has no known cause)
*acne
*hirsutism
*obesity
*hair loss (alopecia)
*velvety, light-brown-to-black, markings usually on the neck, under the arms or in the groin, associated with high insulin levels (acanthosis nigricans).

Circulating androgens arrive at the receptors, enter the cell, and are metabolised to the final, most potent androgens - testosterone which, in turn, is converted by an enzyme called 5 alpha reductase into another form of testosterone called dihydrotestosterone or DHT - the androgen hormone that triggers hair loss in androgenetic alopecia.

This altered androgen metabolism (conversion from weak to potent androgens) is the most common cause of hirsutism and it appears to be the result of an increased conversion in the skin of testosterone to DHT.

Whether a woman is hirsute often is difficult to judge because hair growth varies among individual women and across ethnic groups. What is considered hirsutism in one culture may be considered typical in another. For example, women from the Mediterranean and the Indian subcontinent have more facial and body hair than do women from East Asia, sub-Saharan Africa, and northern Europe.

Dark-haired darkly pigmented whites of either sex tend to be more hirsute than blond or fair-skinned people.

Consideration needs to be given to the increased risks conveyed by long-term androgen excess which include:
infertility
cardiovascular disease
hypertension
osteoporosis
uterine cancer
pituitary adenoma

To some degree, estrogen reduces the effect of androgens in women. Estrogens increase liver manufacture of sex hormone binding globulin (SHBG). Androgens decrease it. Thus lack of estrogens can effectively increase available blood androgens. We see this at menopause when a woman's estrogen levels decline, coinciding with excessive hair sprouting up on her face ... and perhaps less and less of it growing on her head! You can help your body oppose androgen dominance in a number of ways.

*** Progesterone is the one hormone in a woman's body that modulates other hormones helping to restore balance. It's certainly proving to be a major player in the successful treatment of PCOS. Natural Progesterone supplementation might, therefore, be a good starting point.

Natural Progesterone supplementation (NOT synthetic progestin drugs) can have a positive effect on acne that tends to be a by-product of increased androgen production (PCOS). Seborrhea (flaky, itchy skin) clears rapidly with topical progesterone cream, while keratoses (keratinized epithelial cells) are reported to soften and disappear when cream is applied directly to them.

I would certainly suggest women pay particular attention to diet and nutrition, avoid all refined carbohydrates and sugars, introduce a premium phytoestrogen-vitamin-mineral formulation, incorporate a essential fatty acid supplement, get plenty of exercise, drink lots of filtered water, reduce weight (if need be), learn to manage your stress levels, and rest up.

And source yourself a healthcare professional who's familiar with salivary hormone profiles and prescribing human-identical hormone replacement therapy.

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