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R Paradisi

Publications and source records attributed to R Paradisi.

At least 19 recordsLinked to original sources

Longitudinal evaluation of the different gonadotropin pulsatile patterns in anovulatory cycles of young girls.

We studied 13 adolescents (mean gynecological age 29.2 +/- 14.1 months) with anovulatory cycles and 7 women with ovulatory cycles (mean gynecological age 33.1 +/- 15.3 months) as a control group. Adolescents with anovulatory cycles were grouped on the basis of mean plasma LH values: group 1 (n = 7) with high LH values, and group 2 (n = 6) with normal LH values. In all women plasma gonadotropin concentrations were measured at 10-min intervals for 8 h on day 4 of the cycle. Pulsatile gonadotropin secretion was also studied in each subject a second time 40 months later, to establish the outcome of the different pulsatile patterns. Group 1 had more frequent and greater LH pulses than the other two groups (which were similar) and had the highest plasma 17 beta estradiol, testosterone, androstenedione, and 17 hydroxyprogesterone concentrations. Longitudinal control showed that: in group 1, three subjects out of seven acquired ovulatory cycles and there was a fall in mean LH plasma levels (30 +/- 5 vs. 9 +/- 4 IU/L; P less than 0.01), number of pulses (8.3 +/- 1.5 vs. 5 +/- 0; P less than 0.025), mean amplitude (13 +/- 3 vs. 5 +/- 2 IU/L; P less than 0.02) and an increase in interpulse interval (56 +/- 10 vs. 91 +/- 6 min; P less than 0.01). In four subjects anovulatory cycles persisted and the LH pulsatile profile remained unchanged. In group 2, five subjects out of six acquired ovulatory cycles, but there were no significant changes in the number of pulses (6 +/- 1 vs. 6 +/- 2; P = NS), interpulse interval (97 +/- 30 vs. 85 +/- 30 min; P = NS), or amplitude (5 +/- 2 vs. 4 +/- 2 IU/L; P = NS). The results indicate that: 1) anovulatory young women with early normal plasma LH values have an adequate GnRh pulsatile pattern which will easily lead to ovulation; 2) anovulatory young women with high LH plasma values may have a reproductive system blocked in a pathological condition, similar to that observed in polycystic ovary syndrome; 3) only few subjects with high plasma LH values are able to achieve ovulation and normalize LH pulsatile pattern as a consequence of a new mode of GnRh release.

Adolescent

Improvements in automated analysis of catecholamine and related metabolites in biological samples by column-switching high-performance liquid chromatography.

Previously two fully automated methods based on column switching and high-performance liquid chromatography have been described, one for plasma and urinary catecholamines and the other for catecholamine urinary metabolites. Improvements in these methods, after 3 years of routine application, are now reported. The sample processing scheme was changed in order to eliminate memory effects and, in the procedure for plasma catecholamines, a pre-analytical deproteinization step was added which enhances the analytical column lifetime. The applied voltages for the electrochemical detector have been optimized, resulting in an automated method, suitable for the simultaneous determination of vanillylmandelic acid, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid. The sensitivity of the methods allows the detection of 2-3 ng/l of plasma catecholamines and 0.01-0.06 mg/l of urinary metabolites. Also, it is possible to switch from one method to the other in only 30 min. The normal values obtained from 200 healthy people are reported, together with a list of 57 potential interfering substances tested.

Catecholamines

Evidence for a pathological reduction in brain dopamine metabolism in idiopathic hyperprolactinemia.

The role of brain catecholamine activity in the neuroendocrine regulation of the dopamine-PRL system in idiopathic hyperprolactinemia was investigated by high-performance liquid chromatography with electrochemical detector. We measured urinary dopamine, norepinephrine, epinephrine, vanillylmandelic acid, homovanillic acid, 3,4-dihydroxyphenylacetic acid and total 3-methoxy-4-hydroxyphenylglycol levels in 12 women with idiopathic hyperprolactinemia before and during either peripheral dopa-decarboxylase blockade, by carbidopa, or dopamine beta-hydroxylase blockade, by disulfiram. Homovanillic acid and 3,4-dihydroxyphenylacetic acid concentrations were significantly lower (p less than 0.001 and p less than 0.005, respectively) in patients with idiopathic hyperprolactinemia compared with those in 12 control subjects in the early follicular phase, whereas they were similar to those in the control subjects in the pre-ovulatory phase. Dopamine, norepinephrine, epinephrine, vanillylmandelic acid and 3-methoxy-4-hydroxyphenylglycol concentrations were similar to those of the control subjects in both phases of the cycle. During carbidopa administration the levels of all urinary catecholamines and metabolites were unchanged, except that of dopamine which dropped remarkably (p less than 0.001). During disulfiram administration dopamine, homovanillic acid and 3,4-dihydroxyphenylacetic acid concentrations increased (p less than 0.05, p less than 0.001 and p less than 0.005, respectively) and those of norepinephrine, vanillylmandelic acid and 3-methoxy-4-hydroxyphenylglycol decreased (p less than 0.05, p less than 0.001 and p less than 0.005, respectively), whereas epinephrine levels remained unaltered. These data support the existence of a quantitatively reduced brain dopamine activity in idiopathic hyperprolactinemia.

3,4-Dihydroxyphenylacetic Acid

Endocrine and ovarian parameters at various frequencies of ovulation in adolescents.

We assessed ovarian and endocrine function in 86 adolescents over a six month period. Postmenstrual estrone (E1) and estradiol-17 beta (E2) levels, premenstrual FSH levels and pre- and postmenstrual LH, testosterone (T) and androstenedione (A) levels decreased as the frequency of ovulation increased, while premenstrual E2, progesterone (P) and 17 alpha-hydroxyprogesterone levels increased. Both right and left ovarian volume and the per cent of multifollicular ovaries decreased with an increase in the frequency of ovulation. In the premenstrual phase P values correlated significantly with frequency of ovulation for FSH (r = -0.43: P less than 0.001), LH (r = -0.36: P less than 0.01), T (r = -0.31: P less than 0.05) and A (r = -0.26: P less than 0.05). Our data suggest that in the postmenarcheal period the progressive loss of immature endocrine and ovarian characteristics (high LH, FSH, and androgen levels and enlarged, multifollicular ovaries) is linked to an increasing number of ovulations. Progesterone plays a major role in the development of cyclic function characteristic of adult maturity.

17-alpha-Hydroxyprogesterone

Uterine development and endocrine relationships after menarche.

Uterine volume and ovarian/uterine ratio during the first 6 postmenarchal years in 143 women were compared with an adult control group. Plasma gonadotropins and sex steroids were also correlated with uterine volume in adolescents. Uterine volume increased progressively and correlated positively with advancing postmenarchal (r = 0.24; p less than 0.05) and chronologic (r = 0.23; p less than 0.05) age. However, normal adult uterine volume was not yet reached by the highest postmenarchal (6 years) and chronologic (18 years) age. The ovarian/uterine ratio decreased gradually with increasing postmenarchal age but was always higher (0.22) than that of control subjects (0.12). Uterine volume correlated positively with plasma estradiol (r = 0.25; p less than 0.05) and dehydroepiandrosterone (r = 0.22; p less than 0.05) and its sulfate (r = 0.22; p less than 0.05) levels. This study indicates that the uterus continues to grow after menarche in conjunction with increasing hormone levels.

Adolescent

High concentrations of catecholamines in human hypothalamic-hypophysial blood.

While the hypothalamic-hypophysial portal system has been extensively studied in laboratory animals, equivalent studies have not been performed in humans. Here, we present an experimental procedure for collecting suprapituitary blood in man. To solve the question on the origin of such blood we investigated specific markers of hypothalamic secretory activity: the catecholamines (CAs). We found (a) norepinephrine (NE), dopamine (DA), and epinephrine (E) concentrations from approximately 1.5 to 2.5, 3.5 to 4.5, and 6- to 10-fold higher, respectively, in suprapituitary than peripheral blood, (b) different NE/DA and NE/E ratios in favor of DA and E in suprapituitary blood, and (c), a complete (100%) group separation (suprapituitary vs. peripheral) when discriminant analysis included only DA and E. These data indicate that suprapituitary blood composition is different from that of the peripheral blood, and is particularly rich in CAs and claimed differences between DA and E release on one hand and NE release on the other in suprapituitary blood also are observed. We advance the hypothesis of a hypothalamic source of such amines draining via median eminence into portal vasculature, and name this blood "hypothalamic-hypophysial blood." Besides serving as "classical" neurotransmitters, CAs may also have a direct neurohormonal role in the regulation of the human hypothalamic-hypophysial function.

Adult

Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss.

We studied a group of obese hyperandrogenic amenorrheic women to determine the effects of weight loss on anthropometry, hormonal status, menstrual cycles, ovulation, and fertility. Fourteen women had polycystic ovaries, two the hyperandrogenism-insulin resistance-acanthosis nigricans syndrome, one hirsutism of adrenal origin, and three idiopathic chronic anovulation. The duration of amenorrhea before the study ranged from 3-17 months [mean, 8.6 +/- 4.5 (+/- SD)]. All women ate a hypocaloric diet for a period of 8.0 +/- 2.4 months. Weight loss ranged from 4.8 to 15.2 kg (mean, 9.7 +/- 3.1 kg; 1.35 +/- 0.56 kg/month) and the waist to hip ratio, which was used as a measurement of body fat distribution, decreased from 0.86 +/- 0.1 to 0.81 +/- 0.06 (P less than 0.0001). The women's mean plasma testosterone and LH concentrations decreased significantly (P less than 0.001 and P less than 0.005, respectively). A significant positive correlation was found between the decreases in plasma testosterone levels and the decreases in glucose-stimulated insulin levels. Moreover, the decreases in the waist to hip ratio correlated positively with the decreases in glucose-stimulated insulin levels and inversely with the decreases in plasma 17 beta-estradiol. No relationships were found between weight loss and the changes in plasma insulin, steroid, and gonadotropin concentrations. The responsiveness to the weight reduction program was evaluated by comparing the number of menstrual cycles during the study period with the number reported before it. Eight women had significantly improved menstrual cyclicity (responders), while 12 did not (nonresponders). The clinical characteristics and hormone values were similar in responder and nonresponder women. In the group as a whole, 33% of the menstrual cycles during the study were ovulatory, and 4 pregnancies occurred. Hirsutism improved significantly in more than half of the women, as did acanthosis nigricans when present. We conclude that weight loss is beneficial in all obese hyperandrogenic women regardless of the presence of polycystic ovaries, the degree of hyperandrogenism, and the degree and distribution of obesity.

Adult

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/l) (P less than 0.005). LH pulse amplitude was higher than controls (11.6 +/- 3.7 IU/l versus 5.2 +/- 1.8 IU/l; P less than 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 less than 0.02), 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 LH levels was found with the highest hormone values at 1720 h (P less than 0.05) unrelated to apparent sleep and different from that of adult women. Pulse frequency showed a significant slowing during the night with the longest interpulse interval at 0327 h (P less than 0.03) while no significant periodicity was observed in LH pulse amplitude.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Evidence for a hypothalamic alteration of catecholamine metabolism in polycystic ovary syndrome.

The role of brain catecholamine (CA) activity in the neuroendocrine regulation of the GnRH-LH system in polycystic ovary syndrome (PCO) was investigated by high-performance liquid chromatography (HPLC) with electrochemical detector. We measured urinary dopamine (DA), noradrenaline (NA), adrenaline (A), vanillylmandelic acid (VMA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and total 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in a group of 12 women with PCO before and during peripheral dopa-decarboxylase blockade, by carbidopa. HVA and DOPAC concentrations were significantly lower (P less than 0.001 and P less than 0.005, respectively) in PCO patients compared with twelve control subjects in early follicular phase, whereas total MHPG concentrations and MHPG/VMA ratio were significantly higher (P less than 0.005) in PCO patients. Moreover, HVA and DOPAC concentrations in PCO patients were similar to those of the control subjects in preovulatory phase, while MHPG concentrations remained higher in PCO patients (P less than 0.01). DA, NA, A and VMA concentrations were similar to those of control subjects in both phases of the cycle. During carbidopa administration the concentrations of all urinary CAs and metabolites were unchanged, except those of DA which dropped markedly (P less than 0.001). These data suggest that (1) an altered central catecholamine metabolism consisting of DA deficiency and NA excess is present in PCO, and (2) the site of DA deficiency may be located in the hypothalamus.

3,4-Dihydroxyphenylacetic Acid

Insulin as a factor of increased androgen production in women with obesity and polycystic ovaries.

To evaluate the possible role of moderate hyperinsulinemia on abnormal androgen secretion, we examined 4 age and weight-matched groups of obese subjects: 2 groups of women with normal menses whose fasting insulin (IRI) levels were less than or equal to 20 microU/ml (OB-I) or greater than or equal to 40 microU/ml (OB-I) and 2 groups of women with polycystic ovaries who were similarly grouped. All subjects underwent an oral glucose tolerance test, blood sex hormone determination and multiple LH determinations. Compared to OB, OB-PCO women showed significantly higher values of LH, androgen and estrogen concentrations. OB-I and OB-II showed similar hormonal patterns. On the contrary, OB-PCO-II presented significantly (p less than 0.05) higher androstenedione concentrations (348.7 +/- 129.9 ng/dl) (m +/- SD) than OB-PCO-I women (237.0 +/- 73.7 ng/dl). These differences were evident despite similar plasma LH concentrations. In conclusion, these results suggest that insulin may be a factor amplifying LH-dependent androgen secretion in hyperandrogenized women with obesity and PCO.

Androgens

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.

Adolescent

Circadian variations of luteinizing hormone can have two different profiles in adolescent anovulation.

The circadian profile of plasma LH concentrations was investigated in 12 healthy anovulatory adolescent women by drawing blood samples every 20 min for 24 h during the early follicular phase. Plasma 17 beta-estradiol, testosterone, and androstenedione levels were measured in the first sample. Ovarian size was measured by ultrasound. According to their mean plasma LH levels, the adolescents were divided into two groups, those with a high plasma LH level (2 Sd or greater than the mean adult value) and those with a normal plasma LH level. The mean plasma estradiol (P less than 0.001) and testosterone (P less than 0.05) levels were higher in the women with high plasma LH levels compared to those in women with normal plasma LH levels. The LH pulse amplitude was greater (P less than 0.05) and the interpulse interval shorter (P less than 0.025) in the high LH group compared to those in the normal LH group. A 24-h periodicity with the highest plasma LH levels and the greatest pulse amplitude in the afternoon was found in high LH group. In the normal LH group, the highest plasma LH levels and greatest pulse amplitude occurred in the first hours of the morning. An accentuated 24-h LH periodicity is typical of puberty, but disappears in adulthood. We have recorded the persistence of pronounced LH circadian changes in anovulatory adolescent women which might be a marker of a continuing maturational process. Furthermore, LH circadian changes have opposing profiles according to the mean LH values, suggesting the presence of different central nervous system pubertal programs.

Adolescent

Different gonadotropin pulsatile fashions in anovulatory cycles of young girls indicate different maturational pathways in adolescence.

To characterize the spectrum of pulsatile gonadotropin secretion during the postmenarchal period, we studied 24 adolescents whose gynecological age was 1-4 yr. Six women with ovulatory cycles formed a control group. Eighteen women with anovulatory cycles were grouped on the basis of mean plasma LH values: group 1 (n = 8) with high LH values and group 2 (n = 10) with normal LH values. In all women, plasma gonadotropin concentrations were measured at 10-min intervals for 8 h on day 4 of the cycle. Pulsatile gonadotropin secretion was also studied a second time in 7 women from group 1 and 7 from group 2 after 5 days of progesterone (P) in oil treatment to assess the role of P in regulating gonadotropin secretion in the postmenarchal period. Group 1 had more frequent and greater LH pulses than the other two groups (which were very similar) and had the highest plasma 17 beta-estradiol, testosterone (T), androstenedione (A), and 17-hydroxyprogesterone concentrations. In all anovulatory women, basal LH values were correlated with the LH interpulse interval (r = -0.65; P less than 0.01) and pulse amplitude (r = 0.86; P less than 0.001). LH pulse amplitude was correlated with basal 17 beta-estradiol values (r = 0.74; P less than 0.001), and LH interpulse interval with basal T (r = -0.83; P less than 0.001), A (r = -0.51; P less than 0.05), and 17-hydroxyprogesterone (r = -0.79; P less than 0.001) values. P administration decreased LH pulse frequency and increased LH pulse amplitude more in group 2 than in group 1 with high LH values; a clear reduction was also found in A, T, and 5 alpha-dihydrotestosterone values. These results indicate that 1) anovulatory young women with high plasma LH values have an alternative maturational pathway, different from that of anovulatory women with normal plasma LH values, who are similar to ovulatory adolescents; 2) the pulsatile pattern of gonadotropin secretion has specific roles linked separately to amplitude and frequency in controlling ovarian steroidogenesis, which accounts for the endocrine differences between groups; and 3) in the postmenarchal period, by modulating LH and FSH pulsatility and thus reducing androgen levels and their atretic action on follicles, P may be a basic regulatory factor in enhancing functional cyclicity.

Adolescent

Effects of alpha 1-adrenergic blockade on pulsatile luteinizing hormone, follicle-stimulating hormone, and prolactin secretion in polycystic ovary syndrome.

Central noradrenergic mechanisms may participate in the regulation of pulsatile gonadotropin secretion in women with the polycystic ovary syndrome (PCO). To examine this possibility we measured serum LH, FSH, and PRL concentrations at 10-min intervals and total testosterone and 17 beta-estradiol at 60-min intervals for 8 h basally and during the infusion of the alpha 1-adrenoceptor antagonist thymoxamine (10 micrograms/kg X min) in 10 young women with PCO. Mean and integrated serum LH concentrations as well as LH pulse frequency were not significantly altered (P = NS) during the thymoxamine infusion. However, we found an increase in LH pulse amplitude as both net (P less than 0.002) and percent (P less than 0.002) increment, as well as mean LH peak values (P less than 0.05) during alpha 1-adrenergic blockade. There were no significant changes in pulsatile FSH and PRL secretion or gonadal sex steroids during these experimental conditions. These data suggest that in PCO patients, 1) brain noradrenergic mechanisms do not play a stimulatory role in regulating the frequency of pulsatile LH secretion, 2) central noradrenergic activity inhibits LH pulse amplitude, and 3) PRL and FSH pulsatility are not altered by central noradrenergic blockade.

Adolescent

Evidence for a physiological reduction in brain dopamine but not norepinephrine metabolism during the preovulatory phase in normal women.

To investigate the role of brain catecholamine (CA) activity in the mechanisms related to physiological ovulatory function, we used high-performance liquid chromatography with electrochemical detector to measure the levels of urinary dopamine (DA), norepinephrine (NE), epinephrine (E), vanillylmandelic acid (VMA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and total 3-methoxy-4-hydroxy-phenylglycol (MHPG) in a group of 12 normal women during both the early follicular and pre-ovulatory phases of the menstrual cycle. The mean (+/- SEM) concentrations of HVA and DOPAC were significantly lower (P less than 0.001) during the pre-ovulatory phase than during the early follicular phase, whereas those of DA, NE, E, VMA and total MHPG were unaltered. A significant negative correlation between urinary HVA and plasma LH (r = -0.70, P less than 0.01) was also found during the pre-ovulatory period, whereas no significant negative correlations were found between urinary HVA and plasma PRL, progesterone and oestradiol. These data show: 1) reduced brain DA activity and 2) unchanged brain NE activity at the time of the midcycle surge in normal women, suggesting a physiological variation of the central DA metabolism in ovulatory function.

3,4-Dihydroxyphenylacetic Acid

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 beta estradiol (E2) to 25 micrograms (bolus) and 175 micrograms (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 less than 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 less than 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.

Adolescent

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.

Adolescent