Paola Altieri

Polycystic Ovary Syndrome Is a Risk Factor for Type 2 Diabetes: Results From a Long-Term Prospective Study

Polycystic ovary syndrome (PCOS) recently has been identified as a risk factor associated with type 2 diabetes. However, the evidence derives from cross-sectional observational studies, retrospective studies, or short-term prospective studies. This long-term prospective study of a large cohort of women with PCOS, followed from youth to middle age, aimed at estimating, for the first time, the incidence and potential predictors of type 2 diabetes in this population. A total of 255 women with PCOS were followed for at least 10 years (mean follow-up 16.9 years). Six women were patients with diabetes at baseline, and another 42 women developed type 2 diabetes during the follow-up. The incidence rate of type 2 diabetes in the study population was 1.05 per 100 person-years. The age-standardized prevalence of diabetes at the end of follow-up was 39.3%, which is significantly higher with respect to that of the general Italian female population of a similar age (5.8%). The likelihood of developing type 2 diabetes significantly increased as BMI, fasting glucose, and glucose area under the curve at baseline increased and significantly decreased as sex hormone–binding globulin (SHBG) levels at follow-up increased. This study demonstrates that the risk of type 2 diabetes is markedly elevated in middle-aged women with PCOS and suggests including BMI, glucose, and SHBG-circulating levels in the risk stratification.

Effects of Testosterone Undecanoate Administered Alone or in Combination with Letrozole or Dutasteride in Female to Male Transsexuals

INTRODUCTION Testosterone undecanoate (TU) has potential as androgen therapy for ovariectomized female to male (FtM) transsexual subjects; however, the long-term physiologic effects of TU treatment, the significance of testosterone (T), and the T metabolites dihydrotestosterone (DHT) and estradiol (E) on specific outcome parameters are currently unknown. AIM The aim of this study was to investigate the long-term treatment of TU with regard to bone metabolism, body composition, and lipid profile in FtM subjects, and to evaluate the relationship between observed effects and circulating levels of T, E, and DHT. MAIN OUTCOME MEASURES Circulating follicle-stimulating hormone, luteinizing hormone, T, E, DHT, and lipid concentrations were measured, as well as bone metabolism, body composition, and insulin resistance. METHODS This was a 1-year, randomized treatment, open-label, uncontrolled safety study. Fifteen ovariectomized FtM subjects from an outpatient clinic were divided into three groups to receive TU 1,000 mg alone or in combination with oral administration of letrozole (L) 2.5 mg/die or dutasteride (D) 0.5 mg/die for a period of 54 weeks. RESULTS TU alone and TU + D treatments were successful in terms of hormone adjustment, did not result in any adverse effects, and were well-tolerated. Bone mineral density decreased by an average of 0.9 g/cm(2) in the TU + L group, and the addition of D resulted in a failure to gain lean mass. CONCLUSIONS This study confirmed that TU is a successful and safe treatment for FtM subjects. These data indicate that E has an important role in bone metabolism and that DHT may play a role in muscle metabolism.

Bleeding patterns in recent postmenopausal outpatients with uterine myomas: comparison between two regimens of HRT

OBJECTIVES To evaluate and to compare the bleeding patterns obtained with two regimens of hormone replacement therapy given to early postmenopausal women with asymptomatic uterine leiomyomas. METHODS In this randomised prospective 1-year study 50 early postmenopausal women with one to four asymptomatic uterine leiomyomas were enrolled into two study-groups to take two regimens of hormone replacement therapy for 12 28-day cycles: (A) Tibolone, 2.5 mg/day; (B) conjugated equine estrogens (CEE), 0.625 mg/day plus medroxyprogesterone acetate (MPA), 5 mg/day. The bleeding patterns and the changes in uterine volume of the 47 outpatients who completed the study were evaluated and compared. RESULTS Amenorrhea incidence was higher in group A (75.0% of the cycles) than in group B (65.6% of the cycles), while irregular bleeding and irregular spotting incidences were higher in group B (29.7 and 4.7% of the cycles, respectively) compared to group A (22.6 and 2.4% of the cycles, respectively). The mean bleeding and spotting lengths were not statistically different between patients in group A and those in group B. Finally, at the end of the study period transvaginal ultrasonography showed no significant change in leiomyoma size. CONCLUSIONS The results demonstrate that, in early postmenopausal patients with asymptomatic uterine leiomyomas, Tibolone treatment seems to be preferable compared to CEE-MPA continuous combined treatment in relation to the lesser occurrence of irregular bleeding. Furthermore, neither Tibolone nor CEE-MPA therapy, at the doses used here, promote fibroid growth.

Bone density changes in postmenopausal women with the administration of ipriflavone alone or in association with low-dose ERT

Ipriflavone is a synthetic flavonoid that has been shown to exert a direct inhibitory effect on osteoclastic activity and possibly stimulate the osteoblast activity in different experimental models. The aim of the present study was to evaluate the effects of either ipriflavone alone or ipriflavone plus low dose hormone replacement therapy (HRT) in the prevention of postmenopausal bone loss. Patients were randomly allocated to different treatment groups receiving calcium (500 mg/day, control group), continuous HRT (25 or 50 micrograms/day of transdermal 17 beta-estradiol) plus medrogestone 5 mg/day for 12 days/month, ipriflavone at the standard dose of 600 mg/day, or finally ipriflavone 600 mg/day plus 17 beta-estradiol 25 micrograms/day plus medrogestone 5 mg/day for 12 days/month. No significant differences in basal levels of biochemical markers of bone turnover or in basal bone mineral density (BMD) values were evident in the different groups. In the control group after 12 months, spine BMD showed a significant (p < 0.05) 3.41% decrease. The pattern of BMD modification was significantly different from controls in the high dose HRT group (+1.84%), the ipriflavone group (+0.11%), and the combined ipriflavone/HRT group (-0.22%). Conversely, the BMD pattern in the low dose HRT group (-0.55%) was similar to that observed in controls. Thus, present results confirm that ipriflavone and 50 micrograms/day of transdermal 17 beta-estradiol are effective measures in the prevention of postmenopausal osteopenia. A lower transdermal estrogen dose is unable to increase the antiresorptive effect of ipriflavone and did not exert any further action in the prevention of postmenopausal osteopenia.

Body mass index distribution in climacteric women.

Body Mass Index (BMI) was calculated in 2481 climacteric women selected from among the outpatients attending the Menopause Clinic at Bologna University in absence of hormonal replacement therapy and diseases that could cause weight gain. Analysis of variance of the W/H2 (weight/height squared) distribution in different age and climacteric situations demonstrates that the pre-menopause is a weight-gain inducing state and that ageing seems to cause a progressive increase in W/H2.

The Combined Effect of a GnRH Analog in Premenopause plus Postmenopausal Estrogen Deficiency for the Treatment of Uterine Leiomyomas in Perimenopausal Women

Thirty-four perimenopausal women with uterine leiomyomas were treated with intramuscular injections of leuprolide acetate depot each 28 days for 6 cycles, and 12 of them after 168 days of no medication underwent a second 6-month therapy cycle. At the end of the observation period the expected improvement during treatment was maintained at cessation of therapy in 15 patients, due to the effect of the natural postmenopausal estrogen deficiency. Only 3 women underwent hysterectomy, due to the regrowth to baseline values of uterine size. It is concluded that the therapy with gonadotropin-releasing hormone analogs in perimenopause offers an effective alternative to surgery in the treatment of uterine leiomyomas.

Premenopause-Dependent Changes

The authors retrospectively evaluated 1,773 climacteric outpatients in order to establish: (a) criteria able to distinguish different conditions in the transitional phase before menopause (advanced fertile age and premenopause) and (b) premenopause-related changes during the transition from one to the other of several clinical and laboratory parameters. Results showed an increase in gonadotropin plasma levels, a decrease in estrogen plasma levels and a greater frequency of women complaining of hot flushes in premenopause compared to advanced fertile age, as an expression of the progressive decline of ovarian function. Premenopause-related changes were a decrease in thyroid function and an increase in the body mass index, the beginning of bone loss, an increase in glucose, total cholesterol and triglyceride serum levels and a greater frequency of women complaining of hypertension and urinary stress incontinence. An increase in total proteins, uric acid and aminotransferase serum levels was also noted.

Effects of an oral contraceptive combination containing 0.150 mg desogestrel plus 0.020 mg ethinyl estradiol on healthy premenopausal women

SummaryTwenty-six healthy premenopausal outpatients from the Menopause Clinic of the University of Bologna were treated with a combination pill containing 0.020 mg of ethinyl estradiol and 0.150 mg of desogestrel for one year. Throughout the treatment period, clinical and laboratory monitoring was periodically performed, and women were asked about the occurrence of climacteric symptoms. This formulation relieved climacteric symptoms, and did not adversely affect lipids and clotting factors, except for a slight increase in serum triglycerides. Laboratory data also suggest a beneficial effect on bone metabolism.

T04-P-04 Effects of Testosterone Undecanoate (TU) administered alone or in combination with letrozole or dutasteride in Female to Male transsexuals (FtM)

Introduction The role of testosterone (T) and its metabolites, diidrotestosterone (DHT) and estradiol (E), on different physiological functions is not completely known. Ovariectomized FtM T treated represent an interesting model to study the effects of T and its metabolites on different physiological functions. In this study, TU 1000 mg (Nebido ® ) was injected in 15 FtM (week 0, 6,18, 30 and 42) alone (n=5; group A) or in combination with dutasteride 5 mg/d (n=5; group B) or letrozole 5 mg/d (n=5; group C). Results Hormone, bone and metabolic parameters at baseline and at week 54 were: TotalT (nmol/L) GROUP A 7.9±6.0, 13.6±2.6, GROUP B 7.1±6.3, 18.4±4.6§, GROUP C 4.8±4.8, 18.2±4.2§, baseline and wk 54 respectively. E (pmol/L) GROUP A 64.4±43.4, 89.6±36.3, GROUP B 41.4±19.4, 76.0±47.4, GROUP C 37.8±23.1, 18.0±0.0* baseline and wk 54 respectively. DHT (nmol/L) GROUP A 1.3±1.2, 2.2±0.9, GROUP B 1.0±0.7, 0.4±0.1*, GROUP C 0.9±0.7, 2.7±1.3 baseline and wk 54 respectively. *= P §= P No significant changes of any parameters occurred except for bone mass density that significantly decreased in group C and lean mass that increased significantly less in group B as compared to group A. TU injections were well tolerated by all subjects. Conclusions This data suggests that TU is an optimal formulation for replacement in FtM that is well accepted and does not cause major problems. The aromatization of TU is important for maintenance of bone density while DHT may have a role in muscle mass maintenance.

BLEEDING PATTERNS AND COMPLIANCE WITH CEE PLUS MPA CONTINUOUS SEQUENTIAL OR COMBINED REGIMENS IN POSTMENOPAUSAL WOMEN

Transvaginal sonography (TVS) should be performed in order to evaluate endometrial thickness. Endometrial biopsy, if possible under hysteroscopic control, is required whenever endometrial thickness is above 4 mm. Usually, in these cases, pathologic features are found (polyp, hyperplasia, adenocarcinoma). When endometrial thickness is below 4 mm, bleeding and/or spotting (BS) is usually due to altered vascular integrity in the atrophic endometrium.