Roberto Paradisi

Body fat distribution has weight-independent effects on clinical, hormonal, and metabolic features of women with polycystic ovary syndrome

This study was performed to investigate whether different patterns of body fat distribution may have distinct effects on the clinical, hormonal, and metabolic features of women with clinical hyperandrogenism such as polycystic ovary syndrome (PCOS). Ninety-seven consecutive women with PCOS were included in the study after assessment of gynecological and obesity history and careful clinical examination. Women were divided into three tertile groups based on the waist to hip ratio (WHR). Those with peripheral body fat distribution (P-BFD) had a WHR of less than 0.80, those with intermediate body fat distribution (I-BFD) had a WHR of 0.81 to 0.90, and those with abdominal body fat distribution (A-BFD) had a WHR exceeding 0.90. Baseline blood and urine samples were obtained for several hormone and lipid determinations, and the response of glucose, insulin, and C-peptide to a glucose oral challenge (75 g) was investigated. In the PCOS group, WHR values were higher than those used to define P-BFD and A-BFD in the normal female population. As WHR values increased, a significantly greater prevalence of obesity and acanthosis nigricans and a lower prevalence of acne was present. No significant differences were present in any of the other clinical features between the three groups. Ovarian morphology and volumes were similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrasonic findings in polycystic ovarian disease

The uterus and ovaries of 50 patients with polycystic ovarian disease (PCOD) and 30 eumenorrheic women were studied with a real-time ultrasound mechanical sector scanner. Uterine and ovarian volumes (UV and OV) and the OV/UV ratio were calculated, and ovarian morphology was classified as prevalently solid and cystic. Both ovaries were displayed in 44 of the PCOD and in 25 of the normal patients and appeared bilaterally solid, cystic, or with different morphology, respectively, in 43.2%, 47.7%, and 9.1% of cases in the former group and in 76%, 20%, and 4% in the latter group. Statistically significant differences between normal and PCOD patients were found in OV, UV, and OV/UV ratio. Bilaterally enlarged ovaries with multiple tiny cysts, the classic ultrasonographic picture of the polycystic ovary, were found in only 16 (36.3%) of the PCOD cases, while 34 (77.3%) had an OV/UV ratio greater than 1 standard deviation above the mean. Four ultrasonographic ovarian patterns were observed in the PCOD patients: enlarged cystic; enlarged solid; normal-sized cystic; and normal-sized solid. These findings emphasize the need for a reconsideration of the ultrasonographic criteria of PCOD.

Longitudinal Change of Sonographic Ovarian Aspects and Endocrine Parameters in Irregular Cycles of Adolescence

ABSTRACT: We longitudinally studied clinical endocrine and ultrasound parameters of the ovaries in 73 healthy adolescents having persistent menstrual irregularities. After the first examination, they were reexamined after a variable period ranging from 2 to 7 y. During the first examination, three basic features of the ovaries were observed: homogeneous (36%), multifollicular (23%), and polycystic (41%). Polycystic ovaries were most frequent, and they generally exceeded the normal adult range. During the last examination, in the entire group of irregular adolescents, homogeneous ovaries decreased (–14%), polycystic ovaries increased (+ 18%), and a further higher number of subjects exceeded the normal adult range (+10%). The subjects with enlarged ovaries had the highest values of LH, testosterone, and androstenedione. Fourteen subjects out of 46 (30%), with normal ovarian volume in the first examination, registered an ovarian enlargement in the last examination, exceeding the normal range. Moreover, a change from the homogeneous or multifollicular structure to the polycystic one was observed. Twenty-one subjects out of 27 (78%) with enlarged ovaries in the first examination confirmed the high ovarian volume and the unchanged structure in the last examination, whereas six subjects (22%) showed ovaries within the normal adult range; the polycystic structure was substantially confirmed. These results indicate the following. 1) Homogeneous, multifollicular, and polycystic ovaries can usually be found in the postmenarcheal period. 2) Enlarged ovaries, polycystic structure, hyperandrogenemia, and high LH values are strongly linked, and they are frequent in irregular cycles even in the absence of signs of hyperandrogenism. These characteristics may all persist or in various aggregations become a permanent feature. 3) Only a few subjects may lose ovarian enlargement and show a change in the polycystic structure; however, they frequently maintain hyperandrogenemia. 4) During the postmenarcheal period, normal ovarian characteristics may suddenly change, and the ovaries may take on a polycystic structure and increase in volume. Moreover, some endocrine parameters may reach pathologic levels.

Effect of weight loss and antiandrogenic therapy on sex hormone blood levels and insulin resistance in obese patients with polycystic ovaries

This study was performed in two randomly defined groups of obese patients with polycystic ovaries to investigate the overall effects of hypocaloric diet combined (group 2) or not combined (group 1) with an antiandrogenic therapy (cyproterone acetate, 50 mg/day, plus ethinyl estradiol, 0.05 mg/day) on sex hormone plasma levels, insulin secretion and resistance, and body weight loss and on their reciprocal interrelationships. All obese patients with polycystic ovaries showed elevated luteinizing hormone and androgen levels, hyperinsulinemia, and marked insulin resistance. After an average period of 3 months both groups showed a similar weight loss and a similar reduction in the insulin-resistant state. During treatment in group 1 three patients had a greater frequency of menstrual bleeding, and in one of them an ovulatory cycle was documented. Whereas, no changes in gonadotropin and sex steroid levels were found in group 1, a significant fall was observed in group 2. No relationships were observed between these changes and those which occurred on insulin levels. We conclude that hyperandrogenism in obese patients with polycystic ovaries does not appear to be a primary factor leading to the insulin-resistant state.

Insulin and Androgen Relationships with Abdominal Body Fat Distribution in Women with and without Hyperandrogenism

This retrospective study was carried out to investigate, in a large group of hyperandrogenized women with polycystic ovary syndrome (PCOS) and nonhyperandrogenized control women, the interrelationships between sex steroids and indices of body fat distribution. Moreover, we investigated the relationships between these parameters and insulin blood levels, since obese women with abdominal pattern of fat distribution (A-BFD), as well as those with PCOS (either obese and nonobese) are characterized by moderate to severe hyperinsulinemia. A sample of 100 women with PCOS and that of 138 women without clinical signs of hyperandrogenism, who served as a control group, were investigated. The waist to hip circumference ratio (WHR) which was used to define different patterns of fat topography was significantly (p < 0.05) higher in PCOS (0.84 +/- 0.10) than in control women (0.81 +/- 0.08). In both groups, women with WHR values lower than or equal to 0.85 were considered as having a peripheral pattern of body fat distribution (P-BFD) whereas those having WHR values higher than 0.85 had A-BFD. Compared to controls, women with PCOS had higher LH, androgen and estrogen concentrations. In both PCOS and controls there were no differences in sex hormone levels between women with different patterns of fat distribution, except androstenedione, which levels were significantly higher in women with A-BFD than with P-BFD. Women with PCOS showed significantly higher insulin levels than controls. Moreover, in both groups fasting and stimulated insulin were significantly higher in women with A-BFD than in those with P-BFD.(ABSTRACT TRUNCATED AT 250 WORDS)

Postmenarchal evolution of endocrine pattern and ovarian aspects in adolescents with menstrual irregularities.

Ninety-five adolescents with menstrual irregularities persisting since menarche were studied and the data analyzed in relation to gynecologic age. In each year, in the premenstrual phase, luteinizing hormone (LH), testosterone (T), and androstenedione (delta 4A) values were higher than those of adults. Estrone (E1), estradiol (E2), 17-hydroxyprogesterone (17-OHP), progesterone (P), and dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) gradually increased up to adult values correlating with gynecologic age. By ultrasound, nearly half the ovaries were multicystic and ovarian volume was greater than that of adults in each gynecologic year. When the data were classified as ovulatory or anovulatory, ovulation appeared to be a dynamic process characterized by ovaries similar to those of adults and by increasing hormonal levels correlated to gynecologic age. By contrast, in anovulatory cycles, mean T, delta 4A, and LH values were stable in each year and constantly higher than in ovulatory cycles and adult controls. These findings suggest that, despite persistent irregular cycles, some adolescents normalize all endocrine and ovarian parameters toward maturity, while subjects with persistent irregular anovulatory cycles maintain marked hyperandrogenism, increasingly high LH values, and enlarged multicystic ovaries.

EPISODIC PULSATILE SECRETION OF FSH, LH, PROLACTIN, OESTRADIOL, OESTRONE, AND LH CIRCADIAN VARIATIONS IN POLYCYSTIC OVARY SYNDROME

Pulsatile secretion of LH, FSH, PRL, oestradiol and oestrone was studied in a group of 16 patients with micropolycystic ovary syndrome (PCOS) and compared with that of normal ovulatory women in the fifth to sixth day of the cycle. Hormone concentrations were measured at 10 min intervals for 8 h starting at 0930 h. In seven subjects, the study was prolonged for 24 h, with 20 min interval samples, in an attempt to evaluate the circadian rhythm of LH by cosinor analysis. Significant fluctuations occurred in the concentration of each hormone. Values shown are mean ± SD. PCOS subjects had high LH mean values (27.9 ± 5.9 IU/1) (P< 0.005). LH pulse amplitude was higher than controls (11 6 ± 3.7 IU/1 versus 5.2 ± 1.8 IU/1; P<0.005) while no consistent changes in frequency or interpulse interval (62.0±10.7 min versus 65.8 ± 19.2 min; P= NS) were found. A mean of 4.8 ± 1.2 pulses of FSH occurred in 8 h and the mean pulse amplitude was 2.68 ± 1.11 with no differences from controls. All patients were normoprolactinaemic. A mean of 5.5 ± 1.9 pulses occurred in 8 h, the interpulse interval was 76.1 ± 14.4 min and the amplitude was 2.87 ± 0.76 ng/ml and there were no significant differences from controls; 75% of PRL pulses showed a temporal relationship with LH pulses. Oestrone mean basal values were higher in PCOS (47.2 ± 12.5 pg/ml) than controls (32.0 ± 9.9 pg/ml; P<002), while no differences were observed as regards oestradiol. Oestradiol pulse amplitude was nearly the same as oestrone (43.6 ± 18.8 pg/ml and 37.7 ± 16‐1 pg/ml, respectively); 6‐0 ± 2.2 pulses and 6.0 ± 1.6 pulses occurred in 8 h with an interpulse interval of 81.1 ± 27.1 min and 71.8 ± 11.1 min, respectively. Sixty‐five per cent of LH pulses were followed by an oestradiol and oestrone peak. The mean time of the appearance was 17 ± 15 min and 25 ± 23 min, respectively. In the PCOS group a consistent 24 h rhythm in mean plasma

Healthy twins delivered after oocyte cryopreservation and bilateral ovariectomy for ovarian cancer

Anti-neoplastic treatments have significantly increased the survival of cancer patients, but female patients risk premature menopause. Oocyte cryopreservation has been proposed as a fertility-saving option. This report describes the first live birth achieved with autologous cryopreserved oocytes in an ovariectomized borderline cancer patient. A patient with a borderline ovarian tumour asked for oocyte cryopreservation after a right adnexectomy. Ovulation induction resulted in the retrieval and cryopreservation of seven mature oocytes. Thirty-nine months after a left ovariectomy, the patient asked for oocyte thawing and embryo transfer. Endometrial growth was induced using hormone replacement treatment. Three of the seven cryopreserved oocytes were thawed; they survived and, after insemination, normal fertilization took place. Three embryos were transferred into the patients uterus. A twin pregnancy was achieved with the birth of two healthy females. Oocyte cryopreservation may be a reliable option for preserving fertility in young cancer patients who risk premature menopause due to surgery, chemotherapy or radiotherapy.

Menstrual Irregularities in Adolescents: Hormonal Pattern and Ovarian Morphology

The endocrine pattern and ovarian characteristics of 110 healthy adolescents with menstrual irregularities were investigated during the early follicular and premenstrual phases and were compared to those of 14 adolescents with regular menstrual cycles and 20 adults. Over a period of six gynecological years a low ovulation rate (49%) was found in the group of subjects with irregular cycles and regular ovulation was noted in only a few subjects. Slight differences in endocrine pattern and ovarian morphology were observed between the group of adolescents with regular cycles and the group of adults. In contrast, adolescents with irregular menses had higher mean values of luteinizing hormone (LH), testosterone (T), and androstenedione (A) in comparison with the other two groups both in follicular and premenstrual phases. Nearly 35% of the subjects with irregular cycles had levels of T, A and LH which were higher than the upper limit of the adult normal range. Lower progesterone (P), 17P and oestradiol values were observed in the premenstrual phase. Within the group of subjects with irregular menses, LH levels were higher in anovulatory than in ovulatory cycles, in both phases of the cycle, while T and A levels were higher and prolactin levels were lower in the premenstrual phase of anovulatory cycles. Unlike irregular anovulatory cycles, irregular ovulatory cycles showed a hormonal pattern similar to that found in the adult group. By ultrasound evaluation, a high percentage of subjects with irregular menses had multicystic ovaries (57.9%) and the mean (+/- SEM) ovarian volume was higher (10.6 +/- 0.5 cm3) than that found in adolescents with regular menses (6.7 +/- 0.8 cm3) and in the adult group (7.7 +/- 0.3 cm3). With the increase in frequency and continuity of ovulation an improvement in the direction of adult volume and ovarian structure was observed. Besides the endocrine similarity the data emphasize the striking similarity, already documented by histological studies, between pubertal ovaries and those seen in micropolycystic ovary syndrome. These endocrine and ovarian characteristics are typical of a large number of adolescents with irregular menstrual cycles: these features may be representative of a developmental step toward adult normality, although the possibility of a pathological evolution for some subjects cannot be excluded.

Effects of obesity on gonadotropin secretion in patients with polycystic ovarian disease

To investigate the interrelationships between body weight and gonadotropin secretion of polycystic ovarian disease (PCO), basal hormonal pattern and responses of gonadotropins and 17 β estradiol (E2) to 25 μg (bolus) and 175 μg (4-h infusion) of synthetic luteinizing hormone-releasing hormone (LHRH) were studied in two age-matched groups of 18 obese (OB-PCO) and 18 normal-weight (NO-PCO) women suffering from the syndrome. Unlike other hormone levels, plasma LH and the LH/FSH ratio values were significantly higher (p < 0.001) in NO-PCO than in OB-PCO females. Moreover, LH response to both stimuli was significantly greater in NO-PCO with respect to OB-PCO. No differences were found in FSH response, whereas E2 response was significantly higher (p < 0.05) in the NO-PCO group during the continuous infusion test. These results emphasize the role of body weight in the development of PCO in obese females.