Ultrasonography of the ovaries and its correlation with clinical and endocrine parameters in infertile women with PCOS

OBJECTIVES AND METHODS: In 100 anovulatory infertile women with polycystic ovary syndrome attending the infertility clinic of this institute, transvaginal ultrasound findings of ovaries were correlated with both clinical and hormonal parameters using Chi-square test. RESULTS: All women in the study had oligomenorrhea or amenorrhea, 70% had hirsutism and more than half were obese. On transvaginal ultrasound, ovarian volume was more than 10 cm3 in all, 90% had more than 10 follicles in each ovary, 75% had stromal thickness more than 1 cm and more than half had increased stromal echogenicity. Seventy percent had high testosterone levels and 60% were detected to have insulin resistance. Ovarian volume correlated positively with body mass index, waist/hip ratio and menstrual cycle irregularity (p < 0.05). The correlation between ovarian size, LH/FSH ratio and hyperinsulinemia was highly significant (p < 0.005), but was low for serum androgens and also hirsutism. Number of follicles per ovary correlated positively with body mass index, menstrual irregularity (p < 0.01), insulin resistance as well as androgens (p < 0.005). Positive predictive value of ovarian follicle number was 100% for insulin resistance as well as D4 androstenedione. Increased stromal thickness also showed 70% positive prediction for clinical parameters, 66% for insulin resistance and 82% for serum D4 androstenedione. Contrary to the other ultrasound parameters of polycystic ovary, stromal echogenicity did not significantly correlate with any of the clinical or hormonal parameters except serum testosterone. CONCLUSION: Transvaginal ultrasonography of the ovaries confirms the clinical profile and also gives an insight to the hormonal milieu of the women with PCOS.     

Clinical and Biochemical Evaluation of Patients with Hirsutism

Summary: Patients with moderate to severe hirsutism presenting over an 18-month period to an endocrine clinic were assessed by clinical evaluation and hormone measurements. Hair growth rate was estimated by a photographic technique and the severity of hirsutism graded using an objective scale. Of 43 patients, 9 had polycystic ovaries and the remainder were considered to have idiopathic hirsutism. The most severely affected group had significantly increased hair growth rates compared with less clinically affected subjects, and 47% of this group showed objective features of virilization. However, apart from a significantly higher 24-hr urine 17-ketosteroid excretion all other hormonal patterns were not significantly different between severely and mildly affected patients. Serum levels of testosterone (T), sex hormone-binding globulin (SHBG), free T (calculated from T and SHBG values), and androstenedione (A) were abnormal in 44%, 51%, 60% and 60% of patients respectively, whereas plasma levels of the specific adrenal androgen DHAS were increased in 40% of patients. There was an overlap between patients with elevated hormone levels, although isolated elevation of T, A or DHAS were seen in 9%, 19% and 3% of patients respectively. In 19% of patients all serum androgen measurements were normal. Gonadotrophin levels were significantly lower in the more severely affected group. Thus androgen levels in patients with idiopathic hirsutism or polycystic ovaries, show considerable overlap with measurements in normal subjects, and elevated plasma androgens may be of adrenal (DHAS) or combined adrenal/ovarian (T, A) origin.     

Bilateral ovarian thecosis and virilization in pregnancy. A case report

Virilization is usually associated with amenorrhea, infertility and ovarian stromal lesions. Paradoxically, however, it may also be seen in pregnancy; this type of virilization is rare and accompanies ovarian thecosis. Thecosis, also known as thecomatosis and stromal thecosis, is a complex assortment of types of ovarian stromal proliferation associated with various types and amounts of hormonal activity. A patient had progressive virilization that began about seven years after menarche. Nonetheless, she had six pregnancies and bore five normal living children. Her last child, a female, was not affected by the high maternal testosterone levels. The patient's virilization was associated with an ovarian stromal hyperplasia classified as combined thecosis. In this case, as in some others, there was reason to suspect a genetic basis for such progressive virilization with retained fertility; an analysis of it provides insight into the complex nature of ovarian stromal hyperplasia and hormonal activity.     

Pure leydig cell tumour of the ovary in a post-menopausal patient with severe hyperandrogenism and erythrocytosis

A 60-year-old woman, presented with hirsutism, male pattern baldness, deepening voice and plethora over the past 5 years. Hormonal evaluation showed markedly elevated serum testosterone level (>1600?ng/dl) and oestradiol level (220?pg/ml) normal DHEA-SO4 level with suppressed LH and FSH levels. She had markedly erythrocytosis with normal hematological indices. The diagnosis of probable secondary erythrocytosis was made. Trans abdominal ultrasound and CT scan revealed a 14?cm × 11?cm × 9?cm solid pelvic mass. An ovarian androgen secreting tumour was suspected and surgery was performed. Histological examination showed a leydig cell tumour. After the operation testosterone and haematocrit levels returned to normal with regression of clinical symptoms. This is the first case of a leydig cell tumour with an erythropoietic effect of excess testosterone.     

Ovarian mucinous cystadenocarcinoma with virilization

BACKGROUND: Ovarian neoplasms, other than sex cord--stromal tumors, are rare causes of hyperandrogenism. Only two cases of primary mucinous carcinomas associated with virilization have been reported. CASE: A 50-year-old female was referred to our clinic with a large pelvic mass. On examination she had significant facial hirsutism, clitoromegaly, and male pattern pubic hair growth. Serum levels of testosterone and dihydroepiandrosterone sulfate were elevated. A 30-cm, multilocular, solid and cystic, left ovarian mass was resected. Histology revealed moderately to poorly differentiated mucinous cystadenocarcinoma. The ovarian stroma contained florid proliferation of luteinized cells. The right ovary showed cortical stromal hyperplasia. Abnormal hormone values normalized 10 days postoperatively. CONCLUSION: We report a rare case of mucinous cystadenocarcinoma with virilization, review the literature, and discuss the mechanisms of hormone production by these tumors.     

Sclerosing stromal tumor of the ovary: a case report

Sclerozing stromal tumor of the ovary is an extremely rare neoplasm occurring predominantly in the second and third decades of life. Most patients have menstrual irregularities and pelvic pain. Infertility and endometrial pathology have also been described. A 34-year-old woman presented with hirsutism and oligomenorrhea of three months duration. Ultrasound examination showed a heterogeneous right ovarian tumor consisting of predominantly solid tissue with several loculated cysts. On T2-weighted pelvic MR images, signal intensities of the cystic components were high and those of the solid components were heterogeneous, ranging from intermediate-high to high. Dynamic MRI marked early enhancement of solid components in the right ovary. The specimen obtained from endometrial curettage showed proliferative endometrium. Preoperative serum levels of tumor markers were in normal range: preoperative serum levels of testosterone (T) (2.42 ng/ml; normal for adult females 0.1-0.8 ng/ml) and dehydroepiandrosterone-sulphate (DHEA-S) (232.4 microg/dL; normal for adult female, 35-430 microg/dL) were measured and the T value was found increased. At laparotomy, a left ovarian mass was found attached to the right infundibulopelvic ligament and a left oophorectomy was performed. The mass was described as benign by frozen analysis. Definitive histopathological diagnosis was sclerozing stromal tumor of the ovary (SST). The histologic features included a pseudolobular pattern with focal areas of sclerosis and a two-cell population of spindled and polygonal cells. Immunohistochemical studies showed positive smooth muscle actin and negative cytokeratin, keratin, S100 and desmin. The T value decreased postoperatively (0.57 ng/ml).     

Postmenopausal hyperandrogenism of ovarian origin. A clinicopathologic study of four cases.

Postmenopausal hyperandrogenism with overt clinical effects is rare and often related to ovarian stromal disorders. We present a clinicopathologic study of 4 cases. The patients (age range 41-75 years; mean 62 years) had evidence of hirsutism or frank virilization. Their serum testosterone was elevated with or without increases in their serum androstenedione and DHEA levels. There were two right-ovarian hilus cell tumors, one associated with left-ovarian stromal hyperplasia and the other with bilateral hyperthecosis and nodular hilus cell hyperplasia. The other tumor was a small corticomedullary stromal luteoma with bilateral hyperthecosis and nodular hilus cell hyperplasia. The fourth patient had bilateral hilus cell hyperplasia with mild cortical-stromal hyperplasia. All these patients had rapid normalization of androgen levels after surgery without recurrence after a 2- to 10-year follow-up.     

Hirsutism: diagnosis and management

The majority of women with hirsutism have the idiopathic variety characterized by normal circulating androgens. An index of suspicion should, however, be maintained for that subset of women whose hirsutism is indicative of a systemic hormonal aberration. The psychological consequences of this highly visible condition that can seriously impact quality of life substantiate the need for safer and more effective management options. The advent of a topical medication (eflornithine hydrochloride), devoid of systemic side effects, is one positive step toward this goal.     

Ovarian secretion of estrogens in Stein-Leventhal syndrome

Over an 8-year period, 75 Stein-Leventhal patients underwent curettage; 47 of them also had a determination of estrogen secretion. Levels were normal for 49, increased for 16 and were below normal for 10. Endometrial proliferation was found in 33 patients with a total estrogen secretion of 13 mcg/24 hours. Of these 33, 18 also displayed hirsutism. 23% or 17 of the 75 patients showed endometrial hyperplasia but their estrogen secretion was within normal values with the exception of 3 women. Hirsutism was seen in 7 of the patients. An atrophic endometrium was seen in 5 patients, one of whom had a moderate hirsutism; their estrogen levels fluctuated from 10 to 16.5 mcg/24 hours. Hirsutism was the dominant clinical sign in 20 patients with an inactive endometrium and an estrogen level of 10 mcg/24 hours. 17-Ketosteroids and their fractions were independent of the hirsutism and within normal levels. In the absence of ovulation, pregnandiol excretion was low. 48% of the patients with hirsutism (36 cases) did not have estrogen secretion values outside the normal. The results confirm that estrogen secretion in the polycystic ovary does not decrease and that the frequent endometrial hyperplasia is even a direct consequence of persistent estrogen action. That these patients also preserved their female phenotype supports the fact of estrogen sufficiency in the case of the polycystic ovary.     

Virilization in pregnancy due to a borderline mucinous ovarian tumor

Virilization in pregnancy due to borderline mucinous ovarian tumors is very rare. A case of a 28-year-old patient who was noted at 28 weeks' gestation to have marked virilization with raised serum androgens, ascites and a large complex right adnexal mass is presented. Delivery was carried out by cesarean section and at surgery a large tumor was noted in the right ovary. Histology revealed a borderline mucinous ovarian tumor with stromal luteinization, but there was no evidence of stromal invasion. Serum androgens returned to normal levels following surgery and the maternal virilization had resolved at the 6-week postnatal visit. Stromal changes in borderline mucinous ovarian tumors may result in virilization due to androgen production; surgical removal is associated with an excellent clinical outcome.     

Sclerosing stromal cell tumor of the ovary in pregnancy: a case report

A rare case of benign ovarian stromal cell tumor during pregnancy is presented. Because of a rapidly growing solid ovarian mass, 6 x 7 cm in diameter, a 21-year-old woman at 14 weeks of gestation was explored via laparotomy. Histopathological diagnosis was sclerosing stromal tumor of the ovary. She had no complaint of menstrual irregularities before pregnancy and there was no clinical or hormonal evidence of active androgenic hormone secretion. Immunohistochemical staining showed positive vimentin, smooth-muscle actin and desmin reactions. Sclerosing stromal tumor is a very rare condition in pregnancy and our case is only the eighth case detected during pregnancy according to the literature.     

Androgenic adult granulosa cell tumor in a 13-year-old prepubertal patient: a case report and review of the literature.

We report the clinicopathologic findings of an unusual case of adult granulosa cell tumor with androgenic manifestation in a 13-year-old prepubertal girl. The patient had never had a menstrual period and presented with a 1 year history of hirsutism. Physical examination was only remarkable for an increase in facial and abdominal hair, both with a male pattern of distribution. A pelvic ultrasound demonstrated a 6.0 cm right adnexal cyst. Plasma testosterone and 17-hydroxyprogesterone levels were elevated. The patient initially was treated with monophasic oral contraceptive pills for 3 months and owing to lack of response, she underwent an exploratory laparotomy in which a left ovarian tumor, 7.0 cm in greatest dimension, and a 6.5 cm right paratubal cyst were found. A wedge biopsy of the left ovary and subsequent left oophorectomy with right salpingectomy were performed. No gross evidence of disease outside the ovary was noted. Microscopic examination of the left ovarian tumor revealed the typical features of an adult granulosa cell tumor. No tumor was seen outside the ovary. Six days after surgery, plasma testosterone and 17-hydroxyprogesterone levels were in the normal range. Nine months postoperatively, the patient shows no evidence of disease. To our knowledge, this represents the first case of a prepubertal patient with an adult granulosa cell tumor with androgenic manifestations reported in the English literature.     

Uterus didelphys associated with bilateral dermoid cysts and polycystic ovarian disease

A case is reported of bilateral dermoid cysts in a 21-year-old woman with a double uterus, hirsutism, oligomenorrhea and markedly elevated serum-androgens. After surgery her menstrual periods and serum-androgens were normalized, and a histological review revealed polycystic changes just beneath the ovarian capsule. No histopathologic evidence of stromal luteinization was found, but a little group of Sertoli cells was seen in the tumors. On the basis of the case report and the literature, the clinical importance of a definitive diagnosis of polycystic ovarian disease in both the non-surgical and the surgical management of the syndrome is discussed.     

Metformin therapy in women with polycystic ovary syndrome.

OBJECTIVE: To determine the clinical, biochemical, hormonal, and ultrasonographic effects of 6 months of metformin therapy in women with polycystic ovary syndrome (PCOS) and compare with pretherapy parameters. METHOD: 50 Indian women with PCOS, 25 unmarried and 25 married, infertile women, were enrolled in this prospective clinical study. After a baseline workup, including body mass index (BMI), waist hip ratio (WHR), Ferriman Gallwey hirsutism scoring, menstrual pattern, levels of fasting insulin, lipids, oral glucose tolerance test (OGTT), serum gonadotropins, estradiol (E2), testosterone, androstenedione, sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulphate (DHEAS), patients were given 1000 gm of metformin for 6 months and then reevaluated. RESULT: In 41 of 50 women who completed treatment, significant improvement in BMI, WHR, menstrual cyclicity (80.5%), ovulation rate (66%), and pregnancy rate (28%) was noted. Statistically significant decrease in lutenising hormone (LH) and LH/FSH ratio with an increase in follicle stimulating hormone (FSH) levels were seen. Levels of high-density lipoprotein (HDL) cholesterol (Chol) increased along with a decrease in total cholesterol. Improvement was noted in ovarian volume, stromal thickness, and number of follicles. There was no change in hirsutism, acne, levels of other sex steroid hormones, and lipids. CONCLUSION: A 6-month course of metformin therapy may improve menstrual cyclicity and fertility in women with PCOS.     

Finasteride versus cyproterone acetate-estrogen regimens in the treatment of hirsutism.

OBJECTIVES: To compare the clinical and hormonal effects of finasteride and a combination regimen of cyproterone acetate (CPA) plus ethinyl estradiol (EE2) in the treatment of hirsutism. METHODS: Forty hirsute women were enrolled in a prospective randomized trial. Twenty-nine had polycystic ovary syndrome (PCOS) and 11 had idiopathic hirsutism. Patients were randomly treated with finasteride (5 mg/day; n=20) or CPA plus EE2 [CPA (25 mg/day on days 5-14) plus EE2 (20 microg/day on days 5-25) n=20] for 9 months. Main outcome measurement was a reduction in hair growth. Hirsutism score and hormone levels were measured at the beginning and at the end of the study. The student t-test and Mann-Whitney U tests were used for analysis of the data. RESULTS: The modified Ferriman-Gallwey scores for hirsutism decreased significantly at the end of the study from a mean+/-SD of 23.7+/-4.4 to 11.3+/-1.5; P=<0.001 in finasteride group and from 22.3+/-4.2 to 11.4+/-1.2; P=<0.001 in CPA plus EE2 group. Improvement of hirsutism induced by the two treatment methods was similar (47.6 % vs. 51.1%; P=0.2). Treatment with CPA plus EE2 significantly decreased serum total and free T, A, DHEAS, and DHT and increased SHBG levels. Finasteride significantly increased total T but reduced DHT levels. CONCLUSION: Finasteride and CPA plus EE2 are equally effective in decreasing hirsutism, despite significantly different effects on serum hormone levels.     

Virilization due to ovarian hyperthecosis in a postmenopausal woman

A 51-year-old woman presented with hirsutism and virilization of gradual onset. The serum gonadotropin concentrations were in the postmenopausal range, the serum testosterone concentration was markedly elevated (9.8 nmol/l) and the serum estradiol concentration (220 pmol/l) was elevated above the postmenopausal range. A selective venous catheterization study demonstrated raised serum testosterone and androstenedione levels in ovarian veins and suggested the presence of a left ovarian tumor. The raised peripheral estradiol level was shown to be due to ovarian hypersecretion. After bilateral oophorectomy the serum testosterone became normal. Ovarian histology revealed bilateral stromal hyperthecosis. Ovarian hyperthecosis is a rare but important cause of serum testosterone levels in the neoplastic range. This is the third case reported of postmenopausal virilization due to ovarian hyperthecosis and the first report of a selective venous catheterization study in such a patient.     

A rare ovarian Leydig cell tumor (hilar type) causing virilization in a postmenopausal woman

All patients with virilization signs, increased levels of androgen hormones and rapidly progressive hirsutism should be evaluated for an androgen-producing tumor. The ovarian origin of virilization can be suspected by the presence of elevated levels of circulating androgens, with normal levels of cortisol metabolites and a negative dexamethasone suppression test. A case report of a 50-year-old postmenopausal patient with rapidly progressive hirsutism is presented. After an extensive preoperative investigation a right oophorectomy was performed and a Leydig-hilus cell tumor was diagnosed.     

Treatment of hirsutism with lowest-dose flutamide (62.5 mg/day).

Flutamide has been used successfully in the treatment of hirsutism. However, flutamide may cause important side-effects. The aim of this study was to evaluate the clinical and hormonal effects of lowest-dose flutamide therapy. Sixty-one women with hirsutism aged 18-37 years (mean +/- SD 23.4 +/- 5.9 years) were included in the study. Patients received 62.5 mg flutamide once per day for a period of 12 months. A hirsutism score was determined according to a modified Ferriman-Gallwey scoring system. Before therapy, multiscreen blood chemistry, hormonal analysis and complete blood counts were performed. These parameters and hirsutism scores were repeated at 3, 6, 9 and 12 months during therapy. The modified Ferriman-Gallwey scores significantly decreased from 19.1 +/- 4.9 to 5.8 +/- 3.3 during the study (p < 0.0001). The percentage reductions in hirsutism scores (mean +/- SD) were 60.3 +/- 14.4% at 6 months, and 70.3 +/- 13.2% at 12 months. No significant side-effects or modifications in the menstrual cycles were observed. There were no significant differences in any of the hormone levels during therapy. In conclusion, the lowest dose of flutamide, 62.5 mg/day, is a well-tolerated therapeutic agent and can be used in the treatment of hirsutism.     

Prolactin modulates peripheral androgen metabolism

Although hyperprolactinemia may be associated with hyperandrogenism, if hirsutism develops, it is usually a mild form. This study was designed to investigate whether prolactin (PRL) modulates 5 alpha-reductase activity (5 alpha-RA), because 5 alpha-RA is known to be a major factor influencing the manifestation of androgenicity. Compared with normal women, euprolactinemic hirsute and both hyperprolactinemic hirsute and nonhirsute women had elevated levels of unbound testosterone (uT). Serum 3 alpha-androstanediol glucuronide (3 alpha-diol-G) was elevated only in patients who were hirsute, and serum 3 alpha-diol-G/uT ratios were elevated in euprolactinemic hirsute patients and normal in hyperprolactinemic hirsute patients. Genital skin 5 alpha-RA in vitro was elevated only in euprolactinemic hirsute women. The previously recognized positive correlation between 5 alpha-RA and the severity of hirsutism was dissociated with hyperprolactinemia. Human PRL incubated in vitro with normal genital skin also inhibited 5 alpha-RA. These data suggest that PRL modulates 5 alpha-RA and peripheral androgen metabolism and that other factors may also be involved in the evolution of hirsutism in hyperprolactinemia.     

The Clinical Usefulness of 3a-Androstanediol Glucuronide in Premenopausal Women with Hirsutism

Summary: A biochemical parameter correlating with the clinical assessment of the severity of hirsutism and changing appropriately with the clinical response to treatment would be extremely useful. Preliminary reports of androstanediol glucuronide indicated that it was a peripherally-derived androgen and had a high correlation with clinical gradings of hirsutism. More recent reports have cast doubts on this association. This paper presents an evaluation of the clinical usefulness of androstanediol in 121 consecutive premenopausal patients with hirsutism. Androstanediol had a positive correlation with the clinical grading of hirsutism (p < 0.02) and the BMI (p < 0.01) but a negative correlation with age (p<0.01). After adjustment for the effects of age and BMI there was no significant association between the degree of hirsutism and the level of androstanediol. We therefore feel that the routine measurement of androstanediol does not assist in the assessment or management of patients with hirsutism.