Lilliana Ciotta

Clinical and endocrine effects of finasteride, a 5α-reductase inhibitor, in women with idiopathic hirsutism

OBJECTIVE To evaluate the effects of long-term administration of finasteride on hirsutism score, basal gonadotropin, and androgen secretion in women with idiopathic hirsutism. DESIGN Randomized single-blinded study. PATIENTS Eighteen patients with moderate-severe hirsutism were recruited for the study. INTERVENTIONS Nine hirsute patients received 7.5 mg/d oral finasteride for a period of 9 months whereas the other nine were treated with placebo. Hirsutism score, serum basal gonadotropin, androgens, estrogen, and sex hormone-binding globulin (SHBG) levels were evaluated in all patients before treatment and every 3 months during treatment. RESULTS After 6 and 9 months of treatment, the hirsutism score improved significantly in the patients receiving finasteride, whereas no significant modifications were observed in patients treated with placebo. The side effects observed were headache and depression of modest entity during the 1st month of treatments, whereas libido did not change. Serum levels of LH, FSH, androstenedione, unbound T, DHEAS, E2, 17 alpha-hydroxyprogesterone, and SHBG did not change during therapy. Hirsute patients treated with finasteride exhibited a marked decrease of dihydrotestosterone and a significant increase of T serum levels from the 3rd and 6th months of treatment, respectively. CONCLUSION Finasteride decreased the hirsutism score of patients affected by idiopathic hirsutism with few side effects during treatment. No modification of libido was observed.

Treatment of hirsutism with flutamide and a low-dosage oral contraceptive in polycystic ovarian disease patients

OBJECTIVE To evaluate the clinical and hormonal response of the antiandrogen flutamide (Eulexin, Schering Plough, Milan, SA, Italy) associated with a low dosage oral contraceptive (OC) in a group of hirsute women who were unresponsive to OC treatment. DESIGN Twenty-two polycystic ovarian disease (PCOD) patients with hirsutism were treated with flutamide (250 mg twice/d) in association with ethinyl-E2 (0.030 mg/d) plus desogestrel (0.150 mg/d) (Practil 21; Organon, Rome, Italy) for 21 d/mo. SETTING Patients were recruited in the Institute of Obstetrical and Gynaecological Pathology, St. Bambino Hospital, University of Catania, Italy. Hormonal assays were performed in the Hormone Laboratories of St. Bambino Hospital, University of Catania, Catania, Italy. MAIN OUTCOME MEASURE Every 2 months the hirsutism score was evaluated using the Ferriman-Gallwey hair density index. Mean plasma concentrations of LH, FSH, E2, total T, dihydrotestosterone (DHT), androstenedione (A), sex hormone-binding globulin, DHEAS were determined. RESULTS After 8 months treatment with flutamide and low dosage OC, the Ferriman-Gallwey score improved in all patients, mean values decreasing from 25.4 +/- 3.96 to 14.6 +/- 1.92. Plasma levels of total T and E2 were unchanged, whereas LH, FSH, A, and DHT values decreased significantly. Sex hormone-binding globulin levels showed a marked increase. CONCLUSION Flutamide, associated with low dosage OC, favorably influence the hirsutism in PCOD women who are unresponsive to OC treatment alone.

Clinical and hormonal effects of gonadotropin-releasing hormone agonist plus an oral contraceptive in severely hirsute patients with polycystic ovary disease

OBJECTIVE To evaluate the therapeutic effects of a GnRH agonist (GnRH-a), leuprolide acetate (LA) plus a pill containing ethinyl E2 plus cyproterone acetate (CPA) in a group of women with severe hirsutism who were unresponsive to oral contraceptive (OC) therapy. DESIGN Twenty-four patients suffering from severe hirsutism secondary to polycystic ovary disease (PCOD) were treated for 12 months with 3.75 mg IM LA every 28 days in association with 0.035 mg/d ethinyl E2 plus 2 mg/d CPA (Diane; Schering, Berlin, Germany) for 21 d/mo. SETTING Patients were recruited in the Institute of Obstetrics and Gynecology, St. Bambino Hospital, University of Catania, Catania, Italy. Hormonal assays were performed in the Hormone Laboratories of St. Bambino Hospital, University of Catania, Catania, Italy. MAIN OUTCOME MEASURES Every 3 months the hirsutism score was evaluated. Mean serum concentrations of LH, FSH, E2, total and free T, androstenedione (A), sex hormone-binding globulin (SHBG), and DHEAS were determined. Every 6 months a vaginal ultrasound examination was performed. RESULTS In all patients after 6 and 12 months of treatment with LA plus OC, the hirsutism score improved significantly. Serum levels of LH, FSH, E2, total and free T, A, and DHEAS decreased significantly, whereas SHBG showed a marked increase. A significant reduction in the ovarian size was observed. CONCLUSION Gonadotropin-releasing hormone agonist, associated with a pill containing CPA, reduced the hirsutism in severely affected women with PCOD who are unresponsive to OC treatment alone.

Endocrine and Metabolic Effects of Insulin Sensitizers in the Treatment of Patients with Polycystic Ovary Syndrome and Hyperinsulinaemia

We evaluated 16 women with polycystic ovary syndrome (PCOS) and 67 controls, aged 18–34 years. All subjects had an oral glucose tolerance test (OGTT), showing a normal response. They were subdivided into 2 groups (normoinsulinaemic, hyperinsulinaemic) undergoing 7 days of octreotide treatment. This caused modifications in body mass index, waist-hip ratio and blood pressure. No modifications were observed in basal luteinizing hormone (LH), follicle-stimulating hormone, androgens, 17α-hydroxyprogesterone, oestradiol, sex-hormone-binding globulin (SHBG), prolactin and cortisol serum concentrations in normoinsulinaemic patients. A significant decrease in the concentration of LH, androgens, and a significant increase in SHBG were observed in the hyperinsulinaemic patients. In hyperinsulinaemic patients, the treatment restored a regular insulinaemic response to an OGTT. No modifications of glycaemic response were detected in normoinsulinaemic ones. In hyperinsulinaemic patients, a decompensation of the glycaemic response was observed. Several agents (insulin sensitizers) decrease insulin secretion and androgen concentration. They could be considered an approachable long-term therapy for hyperinsulinaemic hyperandrogenic patients. In the next few years the pharmacotherapy for PCOS could be greatly expanded, allowing some patients, such as hyperinsulinaemic ones, to be treated with insulin sensitizers.

Relationship between serum anti-Mullerian hormone and intrafollicular AMH levels in PCOS women

Abstract Polycystic ovary syndrome is a complex disease characterized by various endocrine disorders that are the potential cause of anovulation and hyperandrogenism. Anti-Müllerian hormone expression is suspected to be overexpressed in PCOS granulosa cells. AMH acts as a regulator of folliculogenesis: it is produced by the granulosa cells of follicles from the stage of the primary follicle to the initial formation of the antrum. Serum and intrafollicular AMH levels are elevated in patients with PCOS due to increased number of small follicles and an increased secretion within each of these small follicles. This excess of AMH is strongly suspected to play a role in the characteristic follicular arrest of PCOS, through a negative action on aromatase expression and on FSH action. Value above 5 ng/ml or 35 pmol/l might be considered as a diagnostic criterion for PCOS. The aim of our study is to demonstrate the presence of higher AMH serum levels and higher AMH intrafollicular fluid level of PCOS patients, undergone to IVF cycles, compared to normovulatory patients. The results clearly indicate that blood and intrafollicular AMH levels are significantly higher in PCOS women comparing to the normovulatory population. Serum AMH level appears to be a good predictive marker for the risk ovarian hyperstimulation syndrome: thus, its evaluation should be recommended before starting a controlled ovarian stimulation for IVF.

Effects of myo-inositol, gymnemic acid, and L-methylfolate in polycystic ovary syndrome patients

Abstract Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder, characterized by chronic anovulation/oligomenorrhea, hyperandrogenism, and insulin-resistance. Moreover, some studies propose a possible association between insulin resistance and hyperhomocysteinemia, which is a significant long-term risk for factor for atherogenesis and chronic vascular damage, especially in situations where insulin levels are increased. Insulin-sensitizing agents are used in the treatment of PCOS: in fact, inositols were shown to have insulin-mimetic properties. Synergic action to myo-inositol is that of gymnemic acids that have antidiabetic, anti-sweetener, and anti-inflammatory activities. Gymnemic acid formulations have also been found useful against obesity due to their ability to delay the glucose absorption in the blood. L-methyl-folate increases peripheral sensitivity to insulin, maintaining folatemia stable, and thus restoring normal homocysteine levels. Unlike folic acid, L-methyl folate has a higher bioavailability, no drug/food interferences, high absorption, and it is stable to UV-A exposure. The aim of our study is to compare the clinical, endocrine, and metabolic parameters in 100 PCOS women treated with myo-inositol, gymnemic acid, and l-methylfolate (Group A) or myo inositol and folic acid only (Group B), continuously for 6 months. From a clinical point of view, it was noticed a more significant improvement of the menstrual cycle regularity and a more significant reduction of BMI in Group A. Moreover, a more significant decrease of total testosterone and increase of SHBG serum levels were noticed in Group A. The metabolic assessment found a more significant decrease of total cholesterol and homocysteine levels; OGTT glycemia and insulinemia values were significantly more improved after treatment with myo-inositol + gymnemic acid. In conclusion, we can state that a good option for the treatment of PCOS is the combined administration of myo-inositol + gymnemic acid + l-methyl-folate, especially for overweight/obese patients with marked insulin resistance and with associated hyperhomocysteinemia.

Diagnosis and Assessment

The aim of this chapter is to offer a valid tool to make the diagnosis of polycystic ovary syndrome and to properly assess all the features of a PCOS woman: endocrine, metabolic, and ultrasound parameters are largely described and explained.