Androgen-secreting Ovarian Tumors Research Articles

Case Report: Hyperandrogenism in Menopause.

Postmenopausal androgen excess often occurs due to the imbalance between the rapid decline in ovarian estrogen and a relatively gradual decline in androgen secretion. The rapid onset of hirsutism, alopecia, and acne, on the other hand, is a rare occurrence and requires further investigation in order to rule out an underlying neoplasm. A 54-year-old woman arrived at the endocrinology outpatient clinic for the appearance of hirsutism and defluvium capitis in the past 9 months. She had hypertrichosis of the face, trunk, and mammary areolae and reduced timbre of voice. Circulating androgens were higher than normal levels (testosterone: 7.7 ng/mL, DHEAS: 5437 mcg/L, 17-OH-progesterone: 3.1 nmol/L), gonadotropin and prolactin levels were normal, and Nugent test was negative. Abdominal CT scan was negative for adrenal lesions, while transvaginal ovarian ultrasonography revealed a left adnexal formation (19x18x24 mm) compatible with stromal neoplasm. A bilateral hysteroannessiectomy was performed. Histological examination was diagnostic for multiple ovarian Leydig cell tumors. The most frequent cause of postmenopausal hyperandrogenism is polycystic ovary syndrome. It is necessary to exclude the presence of neoplastic causes (ovarian or adrenal androgen- secreting tumors). In case of marked virilization and severe hyperandrogenism, it is useful to perform transvaginal ultrasonography to search for the presence of ovarian hypertrichosis or androgen-secreting ovarian tumors and a CT/RM scan to study the adrenal glands. The best treatment for hyperandrogenism of neoplastic origin is surgery. Patients who are not candidates for this approach are candidates for therapy with GnRH agonists.

ODP622 A Case of a Rare Steroid Cell Tumor in a Patient with PCOS

Abstract Background Ovarian sex cord-stromal tumors are rare and represent approximately 7% of all primary ovarian tumors. Steroid cell tumors of the ovary are uncommon sex-hormone secreting tumors and are classified as pure stromal tumors. These tumors are known to secrete hormones like androstenedione, alpha-hydroxyprogesterone, and testosterone. Polycystic Ovarian Syndrome (PCOS), a disorder affecting 6% to 10%, is characterized by hyperandrogenism and ovulatory dysfunction. We report a case of a patient with known PCOS who was found to have steroid secreting tumor. Clinical Case A 35 years old female presented to our office complaining of worsening hirsutism, amenorrhea and weight gain. Her past medical history was significant for PCOS, hypothyroidism, and obesity. Physical Examination was notable for hirsutism, obesity and clitoromegaly. Initial labs showed elevated testosterone level of 134 ng/dL (normal levels 0-70 ng/dL). Other labs ruled out congenital adrenal hyperplasia (CAH). Pelvic US was consistent with known PCOS but did not revealed additional findings. Endometrial biopsy was unremarkable. Subsequent labs showed continuous significant elevation in testosterone to 382 ng/dL with free testosterone level of 24 ng/dL. CT abdomen and pelvis with and without contrast showed a right solid adnexal mass. Patient underwent staging laparotomy with bilateral salpingo-oophorectomy. Pathology result was significant for well differentiated sex cord-stromal tumor, steroid secreting type. Genetic testing came positive for BRCA 1. Conclusion This case illustrates that in the setting of rapid onset of hirsutism and elevated testosterone, an androgen secreting ovarian tumor should be considered and ruled out, even in the setting of known PCOS. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP537 A 1.6cm Androgen Secreting Ovarian Leydig Cell Tumor Evades Detection on Multiple Imaging Modalities

Abstract A 1.6cm Androgen Secreting Ovarian Leydig Cell Tumor Evades Detection on Multiple Imaging Modalities Background: Leydig Cell Tumors can present with marked virilization and yet may evade detection with common imaging modalities. This is a case of a patient with hyperandrogenism due to a 1.6cm ovarian Leydig cell tumor that could not be detected on transvaginal ultrasound, contrast enhanced CT or MRI with contrast. Clinical Case: A 61-year woman presented with virilization. She had a history of a right-sided borderline serous ovarian tumor status post right oophorectomy 23 years prior to presentation and a hysterectomy 16 years prior to presentation. She followed up with gynecologic-oncology for several years but eventually stopped as her condition was stable. On re-presenting to establish care with a gynecologist she complained of increased hair growth on her face, abdomen and buttocks as well as hair loss on the front and top of her scalp. On exam, she was noted to have clitoromegaly with no palpable adnexal masses. Labs revealed total testosterone 398ng/dL (8-60ng/dL), free testosterone 9.15ng/dL (0. 06–0.87ng/dL), 17-hydroxyprogesterone 204ng/dL (<51ng/dL) CA-125 of 6.2U/mL (<=38.1U/mL) and DHEAS 23.1mcg/dL (18.9 – 205mcg/dL). Transvaginal ultrasound showed a left ovary of 3cc with no mass or abnormality. She was referred to endocrinology and a CT abdomen and pelvis with contrast was obtained that again showed no adnexal mass but was notable for a 7mm isoattenuating nodule in the left adrenal gland. Additional labs were obtained including 24 hour urinary cortisol and metanephrines, late night salivary cortisol and serum aldosterone and renin activity, all of which were within normal limits. Suspicion remained high for an ovarian source of the hyperandrogenism so a pelvic MRI with and without contrast was performed which showed a normal appearing left ovary measuring 2.3cm×4.2cm×1.8cm. She was referred to gynecologic-oncology and it was decided to proceed with a left oophorectomy. This was performed and the pathology revealed a 1.6cm Leydig cell tumor in the left ovary. Testosterone and 17-hydroxyprogesterone subsequently normalized when checked seven weeks post-op. Conclusion Leydig cell tumors are rare ovarian tumors often presenting with hyperandrogenism in postmenopausal patients and can be difficult to identify on imaging. A review of published case reports revealed 8 cases in which Leydig cell tumors ranging from 1.2cm to 4.6cm could be detected using one of the imaging modalities employed in this case. There were 9 reports of tumors ranging from 0.8cm to 2cm that evaded detection on imaging. When significant hyperandrogenism is present in a postmenopausal patient a strong suspicion for an ovarian source should be maintained even when imaging is apparently normal. Presentation: No date and time listed

PMON224 Newly Observed Interference of Oral Biotin with the Free Testosterone Assay? In a Woman with Postmenopausal Virilization.

Abstract Introduction Approximately 15-20% of US adults take supraphysiologic doses of biotin-containing supplements for common hair and skin problems. When consumed in high doses, competitive and non-competitive immunoassays which use the streptavidin-biotin binding complex can skew results to be either falsely high or falsely low. Case Presentation A 74 y/o Caucasian female who initially presented to her primary care physician concerned for alopecia with frontal balding, acne and moderate hirsutism. Her total testosterone was elevated with 146 ng/dL (7.0–40 ng/dL) with a perplexing normal free testosterone of 4.2 pg/mL (<4.2 pg/mL) in the context of a normal SHBG of 48 nmol/L (14–73 nmol/L). Androstenedione was elevated with 161 ng/dL (17–99 ng/dL) with a normal CMP, prolactin, DHEA-s and 17-hydroxyprogesterone. Transvaginal US was normal. The size of the ovaries was consistent with menopause. Abdominal and pelvic MRI showed normal adrenal glands and ovaries. She was taking between 1 to 3mg of biotin per day. Biotin was discontinued. Repeat testing revealed an elevated free testosterone of 12.7 pg/mL (0.2 - 3.7 pg/mL) along with an elevated total testosterone of 120 ng/dL (2 - 45 ng/dL) and a normal SHBG of 39 nmol/L (14–73 nmol/L) which was now consistent with her clinical picture of postmenopausal hyperandrogenism. Bilateral laparoscopic salpingo-oophorectomy was recommended to exclude an androgen-secreting ovarian tumor or hyperthecosis. Testing was then repeated while taking biotin which again manifested a normal free testosterone of 2.8 pg/mL (<4.2 pg/mL) with an elevated total testosterone of 121.4 ng/dL (7.0–40 ng/dL) and a normal SHBG of 45 nmol/L (14–73 nmol/L). Discussion Biotin may interfere with the total testosterone levels, but little is known of its effects on free testosterone. We report the first case of biotin interference on the free testosterone assay, resulting in falsely low values demonstrated in two different occasions, that improved following withdrawal of this widely used vitamin supplement. Laboratories use a direct analog enzyme immunoassay to calculate the free testosterone however its calibration and specificity has been debatable, and it is still unclear how biotin can affect it. It is critical that laboratorians and clinicians are aware of this biotin interference so that misdiagnosis and inappropriate treatment can be prevented.

Non-PCOS Hyperandrogenic Disorders in Adolescents

Hyperandrogenism-clinical features resulting from increased androgen production and/or action-is not uncommon in peripubertal girls. Hyperandrogenism affects 3 to 20% of adolescent girls and often is associated with hyperandrogenemia. In prepubertal girls, the most common etiologies of androgen excess are premature adrenarche (60%) and congenital adrenal hyperplasia (CAH; 4%). In pubertal girls, polycystic ovary syndrome (PCOS; 20-40%) and CAH (14%) are the most common diagnoses related to androgen excess. Androgen-secreting ovarian or adrenal tumors are rare (0.2%). Early pubic hair, acne, and/or hirsutism are the most common clinical manifestations, but signs of overt virilization in adolescent girls-rapid progression of pubic hair or hirsutism, clitoromegaly, voice deepening, severe cystic acne, growth acceleration, increased muscle mass, and bone age advancement past height age-should prompt detailed evaluation. This article addresses the clinical manifestations of and management considerations for non-PCOS-related hyperandrogenism in adolescent girls. We propose an algorithm to aid diagnostic evaluation of androgen excess in this specific patient population.

Hirsutizmli Hastada Sertoli Leyding Hücreli Over Tümörü

Hiperandrojenizm; kadınlarda hirsutizm, akne, alopesi gibi belirtilere neden olan androjen fazlalığı durumudur. Hirsutizm ise kadınlarda androjene duyarlı bölgelerde erkek tipi kıllanma artışıdır. Hiperandrojenizmin birçok nedeni bulunmaktadır. Androjen salgılayan over ve adrenal tümörler hiperandrojenizmin nadir görülen nedenlerindendir. Özellikle klinik tablonun hızlı ilerlediği, virilizasyon bulgularının eşlik ettiği androjen düzeylerinin çok yüksek olduğu olgularda over ya da adrenal kaynaklı tümörler akla gelmelidir. İzole total testosteron düzeyi 4,15 ng/mL olan ve görüntülemede lezyon saptanmayan postmenopozal kadın hastada bilateral ooforektomi sonrası hiperandrojenizmin nadir bir nedeni sertoli leyding hücreli over tümör tanısı konuldu.

Androgenic Granulosa Cell Tumor in an Adolescent Girl

Virilizing tumors may arise from adrenals or ovary. Androgen secreting ovarian tumors constitute less than 0.2% of cases of hyperandrogenism and less than 1% of all ovarian tumors. Hyperandrogenism is seen with Leydig cell tumors, Sertoli cell tumors, steroid cell tumors not otherwise specified and ovarian thecomas. Adult granulosa cell tumors (GCTs) are the most common type of ovarian sex cord tumors. These tumors usually produce estrogens and hence cause symptoms and signs of estrogen excess. GCTs mostly present in perimenopausal and postmenopausal women with complaints of abnormal uterine bleeding. Androgen secreting GCT is a rare clinical entity. Here we are reporting one such case in an adolescent girl with features of hyperandrogenism and ovarian mass.

SUN-005 Hirsutism Due to Bilateral Leydig Cell Tumors

Severe hyperandrogenism in post-menopausal women is rare. It may be caused by either benign or malignant neoplasms of the adrenal or ovary. We report a rare case of a post-menopausal woman with hirsutism associated with virilization due to Leydig cell tumors (LCT) of both ovaries. Case report 61 yo female presented for evaluation of hirsutism. She had also been experiencing increased facial hair growth, deepening of voice, clitoromegaly, alopecia, and acne. Physical examination: normal vital signs. Patient had signs of virilization, including coarse hair along her upper lip, chin, lower abdomen and inner thigh with Ferriman-Gallwey score of 8, acne, and clitoromegaly. She had no signs of acanthosis nigricans or Cushing syndrome. Base line labs: Hemoglobin 16.2 gm/dL (ref 12.0 to 15.5), total testosterone 803 ng/dL (ref 3–41), free testosterone 20.2 pg/mL (ref 0.0–4.2), estradiol 77 pg/mL (<6.0−54.7), estrone 148 pg/mL (ref 7–40), FSH 11.5 mIU/mL (ref 25.8 - 134.8), LH 6.90 mIU/mL (ref 7.7 - 58.5), androstenedione 28 ng/dL (ref 17–99), DHEAS 99.9 mcg/dL (ref 19–205), dehydroepiandrosterone 512 ng/dL (ref 31–701), inhibin A 2.3 pg/mL (ref <5), inhibin B <7.0 pg/mL (ref 00-16.9), 17-alpha hydroxyprogesterone 187 ng/dl (ref <51). Her other serum markers such as anti -Mullerian hormone, alpha-fetoprotein, and hCG were normal. A CT scan of adrenals: normal. Similarly a transvaginal US did not show any ovarian pathology, however MRI of the pelvis showed homogeneous ovarian enhancement bilaterally and based on this information a diagnosis of ovarian hyperthecosis was considered and patient underwent laparoscopic bilateral oophorectomy. Pathology confirmed: LCT in both ovaries. Laboratory values performed 3 months later showed the following values: hemoglobin 14.2 gm/dL, total testosterone 13 ng/dL, free testosterone 1.4 pg/mL, LH 124 mIU/mL, FSH 99mIU/mL, estradiol <5.0 pg/mL. In 6 months she had significant improvement in hirsutism and virilization. Discussion Hyperandrogenism, especially serum testosterone in the male range with rapidly progressive hirsutism or virilization signs in a female indicates tumor etiology. Androgen-secreting ovarian tumors are usually small and often embedded in the ovary. Transvaginal US is useful in the diagnosis of ovarian tumors. However, in our case, transvaginal US failed while MRI scan showed bilaterally enlarged ovaries and with this information patient underwent bilateral oophorectomy. Although 5 cases of bilateral LCT are reported in the literature, LCT is unilateral 95% of the time, the pathogenesis of Leydig cell proliferation and LCT is unclear. In conclusion, androgen secreting tumors should be considered in women (especially in post-menopausal state) with hyperandrogenism and hirsutism. In fact, diffuse stromal Leydig cell hyperplasia and small Leydig cell tumors may be missed on imaging and in some cases only pathology can confirm the result.

Virilizing ovarian tumor: the challenges of differential diagnosis

SertoliLeydig cell tumor is a rather rare type of ovarian neoplasms belonging to the group of sex cordstromal tumors. This malignancy is characterized by androgen overproduction, which results in the so-called virilization and can be accompanied by various metabolic disorders such as abdominal obesity, disturbances of carbohydrate and protein metabolism, and high blood pressure. During differential diagnosis, it is important to identify the source of androgen overproduction. An androgen-secreting ovarian tumor needs to be differentiated from androgen-secreting adrenal tumor, ovarian stromal thecomatosis (hyperthecosis), and endogenous hypercorticism (the Cushings syndrome). In most cases, the SertoliLeydig cell tumor is associated with DICER1 mutation carriership. If a patient is found to carry the DICER1 mutation, patients relatives need to undergo genetic testing as the individuals with mutations in this gene have an elevated risk of developing a broad range of benign and malignant tumors (most of these tumors are relatively rare in the overall population). The awareness of this rare ovarian neoplasm among medical specialists (obstetriciansgynecologists, endocrinologists, and oncologists) is supposed to ensure timely diagnosis and adequate treatment of this disease.

Androgen-Secreting Ovarian Tumors.

About 1% of ovarian tumors that comprise testicular cell types can cause hyperandrogenism followed by characteristic virilization. Androgenic group of tumors originated mainly from sex-cord stromal ovarian tumors are including steroid cell tumors, Leydig tumors, granulosa cell tumors, Sertoli cell tumors, Sertoli-Leydig cell tumors, gonadoblastomas, and some other rare forms as ovarian metastases from neuroendocrine tumors. Germline or somatic mutations in some genes like DICER1, STK11, and FOXL2 are associated with the development of some sex cord-stromal ovarian tumors. Basal serum testosterone concentrations above 7 nmol/L could indicate an androgen-secreting tumor. Other ovarian and adrenal androgens should be determined and functional endocrine testing including low-dose dexamethasone suppression test, gonadotrophin-releasing hormone (GnRH) agonist test, imaging methods, and selective venous sampling should be performed. Surgery is the first-line treatment for most of the tumors. Women who are not good surgical candidates could benefit from use of GnRH agonist to control hyperandrogenism. In some cases, chemotherapy and/or radiation therapy is required while some tumors respond on antiangiogenic agents used alone or in combination with chemotherapy. Metabolic implications and long-term outcomes of ovarian androgen-secreting tumors are unknown and require more detailed follow-up in multicentric and longitudinal clinical studies.

Virilizácia ako prejav hypertestosteronizmu pri ovariálnom tumore: kazuistika

Hypertestosteronism as part of hyperandrogenic states in women is generally defined as abundance of male hormones (in this case abundance of testosterone). Spectrum of clinical symptoms include menstrual disorders, amenorrhoea, different range of hirsutism and virilization. Statistically, most androgen secreting tumors are ovarian aetiology (testosterone secreting tumors located in suprarenal gland are very rare). This rare tumor may produce excess amounts of testosterone, as well as its precursor androstenedione. The highest incidence is between 20-40 years and in postmenopausal period. The treatment is essentially surgical; with gradual adjustment of the hormones.Key words: androgen secreting ovarian tumors - hyperandrogenic states - testosterone - virilisation.

“Occult” ovarian Leydig cell tumor: when laboratory tells more than imaging

Hyperandrogenism is a common finding in premenopausal age and is generally caused by polycystic ovarian syndrome or other benign disease. Androgen-secreting tumors represent only 0.2 % of the causes of hyperandrogenism and usually present with severe clinical features, abrupt onset, and very high androgens levels. We describe here three cases of occult ovarian Leydig cell tumors suspected on the basis of severe clinical features of hyperandrogenism rapidly worsening, with elevated serum total testosterone levels, in which bilateral ovariectomy was performed and tumor was confirmed by post-operative histology. In all three cases, imaging was negative for ovarian tumor. Moreover, in one case the confounding concomitant finding of bilateral adrenal masses posed an additional challenge. Our experience highlights that testosterone levels represent the most helpful marker in the diagnosis of androgen-secreting ovarian tumor. In the absence of imaging findings, bilateral ovariectomy should be indicated, if supported by unequivocal clinical and laboratory data.

Síndrome hiperandrogênica em mulher na pós-menopausa: relato de caso

Hyperandrogenic syndromes include diseases that manifest through an increased biological activity of androgens and that can originate from neoplastic or functional diseases. Androgen-secreting ovarian tumors represent about 1% of ovarian neoplasias. Steroid cell tumors are among the more rare types which account for less than 0.1% of all ovarian tumors. They are usually benign, of small dimensions and unilateral. We report here a rare case of a unilateral steroid cell tumor. A 60-year-old woman was seen after four months of evolution of hirsutism, clitoris hypertrophy and elevation of serum estradiol levels. Her total testosterone and 17-OH-progesterone levels were also increased.

Virilización en una mujer posmenopáusica. Consideraciones diagnósticas y terapéuticas

Virilizing tumors are rare disorders that commonly develop in the adrenal cortex or the ovaries. Because these tumors are usually millimetric, androgen-secreting ovarian tumors can be particularly difficult to identify through commonly available imaging techniques and can thus pose a diagnostic challenge. We present the case of a 71-year-old woman who presented with severe clinical hyperandrogenism and biochemical traits suggestive of an ovarian source but who was diagnosed with a 10-cm adrenal mass.

Hirsutism in a Fifty-Eight-Year-Old Woman

Abstract: Hirsutism is the presence of excess terminal hair in females in a male-like pattern. Although there are several causes of hirsutism, androgen-secreting ovarian tumors are presumed to be a rare cause of hirsutism. Here we submit the case report of a female who presented with hirsutism and was eventually found to have an ovarian tumor secreting androgen.

The Current Role of Venous Sampling in the Localization of Endocrine Disease

Endocrine venous sampling plays a specific role in the diagnosis of endocrine disorders. In this article, we cover inferior petrosal sinus sampling, selective parathyroid venous sampling, hepatic venous sampling with arterial stimulation, adrenal venous sampling, and ovarian venous sampling. We review their indications and the scientific evidence justifying these indications in the diagnosis and management of Cushing's syndrome, hyperparathyroidism, pancreatic endocrine tumors, Conn's syndrome, primary hyperaldosteronism, pheochromocytomas, and androgen-secreting ovarian tumors. For each sampling technique, we compare its diagnostic accuracy with that of other imaging techniques and, where possible, look at how it impacts patient management. Finally, we incorporate venous sampling into diagnostic algorithms used at our institution.

Androgen-Secreting Steroid Cell Tumor of the Ovary*

We present the case of a 93-year-old virilized woman with an androgen-secreting ovarian tumor. This rare ovarian sex cord stromal tumor behaved in a malignant fashion. Various aspects of the presentation, diagnosis, and treatment of these tumors are discussed.

The Effects of Long Term Testosterone Administration on Pulsatile Luteinizing Hormone Secretion and on Ovarian Histology in Eugonadal Female to Male Transsexual Subjects

Polycystic ovarian disease (PCOD) is associated with elevated serum LH and (sub)normal FSH levels, while serum androgen levels are often elevated. To clarify the role of androgens in this abnormal pattern of gonadotropin secretion, LH secretion was studied in 1) 9 eugonadal female to male transsexual subjects before and during long term (6 months) testosterone (T) administration (250 mg/2 weeks, im), and 2) in a woman with an androgen-secreting ovarian tumor both before and after surgical removal of the tumor. Finally, we studied the effects of high serum androgen levels on ovarian histology in 3) 26 transsexual subjects after long term (9-36 months) T administration (250 mg/2 weeks, im) to assess whether T-induced ovarian abnormalities are similar to those that occur in women with PCOD. Long term T treatment in the nine female to male transsexual subjects resulted in increases in the mean serum T level from 1.7 +/- 0.8 (+/- SD) to 40.8 +/- 31.9 nmol/L (P less than 0.01), the mean serum dihydrotestosterone level from 0.6 +/- 0.2 to 3.3 +/- 1.5 nmol/L (P less than 0.02), and the mean serum free T level from 9.5 +/- 5.2 to 149 +/- 46 pmol/L (P less than 0.02). Mean serum estrone and estradiol levels were similar before and during T treatment. The mean serum LH level decreased from 6.3 +/- 2.0 to 2.9 +/- 1.1 U/L (P less than 0.01), and the mean FSH levels decreased from 6.6 +/- 2.0 to 3.7 +/- 2.2 U/L (P less than 0.02). Pulsatile LH secretion before and during T treatment was studied in five subjects. Neither the mean nadir LH interval nor the LH pulse amplitude changed significantly in these five subjects. The serum T level in the woman with the androgen-secreting ovarian tumor was 9.6 nmol/L, and it declined to normal after removal of the tumor. Her mean serum LH and FSH levels, the mean nadir LH interval, and LH pulse amplitude were in the normal range before and after removal of the tumor. Studies of ovarian histopathology in 26 transsexual subjects after long term androgen treatment revealed multiple cystic follicles in 18 subjects (69.2%), diffuse ovarian stromal hyperplasia in 21 subjects (80.8%), collagenization of the tunica albuginea in 25 subjects (96.2%), and luteinization of stromal cells in 7 subjects (26.9%). Findings consistent with criteria for the pathological diagnosis of polycystic ovaries, that is 3 of the 4 findings listed above, were present in 18 of the 26 subjects (69.2%).(ABSTRACT TRUNCATED AT 400 WORDS)

The diagnostic value of plasma free testosterone in non-tumorous and tumorous hyperandrogenism

The clinical significance of total and free testosterone (T) estimates for the diagnostic approach to hirsute patients was assessed. Plasma T was measured by radioimmunoassay and its non-protein-bound fraction was determined by equilibrium dialysis, thus facilitating the calculation of apparent free T (AFT). The cases of 162 subjects were investigated; the subjects included 75 women in whom glandular androgen release had been defined by selective catheterization. A positive linear correlation was observed between both parameters over a wide range of concentrations (T, 153 to 10,700 pg/ml; AFT, 0.8 to 342 pg/ml; P less than 0.001). Significant differences of mean T and AFT levels were found between healthy control subjects (n = 8) and subjects with non-tumorous hyperandrogenism (n = 60; P less than 0.005). Individual values overlapped considerably; elevated T (greater than 640 pg/ml; 48%) or AFT (greater than 7.2 pg/ml; 52%) were present in only half the hirsute women. However, the upper 95% confidence limits of normal for both indices were exceeded in all patients with androgen-secreting ovarian tumors (n = 7). It is concluded that the indirect estimation of AFT in addition to T is time-consuming, costly, without practical value in selecting the proper treatment, and therefore not mandatory in the routine evaluation of androgenized women.