L. Anttila

Clinical features and circulating gonadotropin, insulin, and androgen interactions in women with polycystic ovarian disease *

Objective To investigate the interactions of hyperinsulinemia and inappropriate gonadotropin secretion in women with polycystic ovarian disease (PCOD). Design Comparative study of endocrinologic parameters in subjects with PCOD. Setting Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. Patients Fourteen nonobese and 10 obese patients with PCOD. Seven healthy women for reference data collection. Normal thyroid function, serum prolactin concentration, normal diurnal cortisol variation, euglycemia in all subjects. Main Outcome Measures Serum concentrations of insulin, testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, immunoreactive luteinizing hormone (LH), bioactive LH, and follicle-stimulating hormone (FSH). Results The concentration of insulin was higher and that of bioactive LH was lower in obese than in nonobese PCOD women in whom the levels were also above the upper reference value. There was a negative correlation between insulin and bioactive LH levels (r = —0.57). Bioactive LH correlated inversely with the body mass index (BMI) (r = —0.50). After eliminating the effect of the BMI, the correlation between bioactive LH and insulin was no longer significant (r = —0.37). The bioactive LH and immunoreactive LH/FSH ratio correlated significantly (r = 0.68). Conclusions These data demonstrate that hyperandrogenic women can be divided into two subgroups: those with insulin resistance, normal or minimally elevated LH, and markedly elevated insulin levels; and those with elevated LH levels, no insulin resistance, and normal insulin concentrations. Obesity is associated with the former, and high bioactive LH levels with the latter subgroup.

Expression of syndecan-1 in human placenta and decidua

Syndecan-1 is a cell surface heparan sulphate proteoglycan, which binds to the extracellular matrix (ECM), growth factors and antithrombin III. The early expression of syndecan-1 during mouse embryonic development suggests a potential role in the communication between the embryo and the ECM of decidua. Using immunohistochemical methods, the present study showed that the expression of syndecan-1 in the trophoblast cells changes along trophoblast differentiation. The syncytiotrophoblasts in the chorionic villi exhibited an apical expression of syndecan-1. This suggests that the expression is restricted to non-migrating, non-proliferating trophoblasts. The mode of syndecan-1 expression by human placental trophoblasts is independent of gestational age. The expression is not changed in miscarriages. In pre-eclampsia, the staining for syndecan-1 on the villous syncytiotrophoblast is weaker compared to normal pregnancy, but in placental bed the expression is similar. The unique apical localization of syndecan-1 in chorionic villi, not detected in any other tissues, suggests a potential role in fetomaternal communication probably via growth factor binding and in anticoagulation of intervillous circulation.

Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries *

OBJECTIVE To examine the effect of short-term progestogen treatment on androgen, gonadotropin, and sex hormone-binding globulin (SHBG) levels in oligomenorrheic women. DESIGN Comparative study of changes in hormonal parameters in patients with or without ultrasonographically diagnosed polycystic ovarian disease (PCOD). SETTING Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. PATIENTS Seventy-five oligomenorrheic women with (n = 51) or without (n = 24) PCOD. MAIN OUTCOME MEASURES Serum concentrations of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG. RESULTS The levels of T, A, LH, and the LH:FSH ratios decreased significantly after oral treatment with medroxyprogesterone acetate (10 mg/d for 10 days) in non-PCOD women and in women with PCOD decreasing the frequencies of pathological laboratory findings, in particular elevated levels of LH:FSH ratio and A in PCOD women and of LH:FSH ratio in non-PCOD women. The levels of T, A, and LH as well as the LH:FSH ratio were significantly higher in women with PCOD. Obesity was associated with high free androgen indices, low LH:FSH ratios, and low concentrations of LH, A, and SHBG. CONCLUSIONS The serum samples for hormonal analyses used as an aid in diagnosing PCOD should be obtained without pretreatment with progestogen because it masks the biochemical findings of PCOD.

Hormonal responses to physical exercise in patients with polycystic ovarian syndrome

OBJECTIVE To examine the effects of obesity and polycystic ovarian syndrome (PCOS) on the endocrine responses to physical exercise. SETTING Outpatient clinic of reproductive endocrinology at the University Central Hospital of Turku and the Department of Pharmacology, University of Turku, Turku, Finland. PATIENTS Nine oligomenorrheic women with PCOS (body mass index [BMI] 19.5 to 46.0 kg/m2) and eight control women with regular menstrual cycles (BMI 20.0 to 53.5 kg/m2). INTERVENTIONS A bicycle ergometer test was performed at 8 A.M. RESULTS The only hormone response that was different between PCOS patients and controls was the exercise-induced increase in circulating GH levels. This response was significantly greater in controls than in PCOS patients. There was also a negative correlation between the GH response and BMI. The increases in the concentrations of adrenaline, noradrenaline, 3,4-dihydroxyphenylglycol, glucose, and insulin:C-peptide ratios during the bicycle ergometer test were correlated negatively to BMI. CONCLUSION Obesity is an important determinant of the hormonal responses to physical exercise. This applies also to women with PCOS. Taking obesity into account in the analysis of exercise-induced hormone responses, only little, if any, of the variation in the hormonal responses measured by us could be attributed to PCOS per se. The only hormone response that was different between PCOS patients and controls was the GH response.

Neither exogenous nor endogenous GnRH stimulation alters the bio/immuno ratio of serum LH in healthy women and in polycystic ovarian disease

The purpose of this study was to re‐evaluate the quantitative and qualitative responses of LH to exogenous and endogenous GnRH stimulation in normally cycling women and in polycystic ovarian disease (PCOD). Responses of serum LH to GnRH (100g i.v.) and the opioid antagonist naloxone (10 mg i.v.) were determined in healthy women in the early (n = 5) and late (n = 4) follicular phase, and in patients with PCOD (n = 20). Serum bioactive (B) LH was determined by a mouse interstitial cell in vitro bioassay, and immunoreactive LH by a conventional RIA (I‐LH) and a novel sensitive (0.05 IU/I) and specific immunofluorimetric assay (F‐LH). The B/I (2.4 ± 0.1) and B/F (2.7 ± 0.6) ratios in basal serum samples of the PCOD patients were significantly higher (p < 0.05) than the corresponding ratios (1.6‐1.8 and 1.8‐2.0) of the control women. GnRH stimulated the secretion of I‐LH (2‐4‐fold), F‐LH and B‐LH (3‐5‐fold each) in all groups studied. There were no apparent changes of the BII and BIF ratios in normal women during early follicular phase or in patients with PCOD. However, the normal women during late follicular phase displayed a significant (pCO.05) increase in the BII ratio, albeit no change was found in the BIF ratio. During naloxone‐induced endogenous GnRH responses, the control women during late follicular phase showed a %‐fold increase in B‐LH, I‐LH and F‐LH, with unchanged B/I and B/F ratios. No LH responses to naloxone were found in normal women during early follicular phase or in patients with PCOD. We conclude that, hy utilizing an immunofluorimetric assay, the basally elevated biohmmuno ratio of LH could be confirmed in PCOD patients. However, there were no qualitative changes in LH during the response to GnRH stimulation in normal women or in PCOD.

Adrenal- and Ovarian-Vein Steroids and LH Response to GnRH in Two Patients with Virilizing Adrenocortical Adenoma Studied by Selective Catheterizations

Two women with androgen-secreting adrenal adenomas were studied by selective adrenal- and ovarian-vein catheterization. Blood samples were collected for determination of testosterone, androstenedione, dehydroepiandrosterone sulfate and cortisol. In a preoperative stimulation test with gonadotropin-releasing hormone, the response of luteinizing hormone was enhanced in both subjects. In catheterization studies, the venous gradients for the hormones were not diagnostic for the source of hyperandrogenism in either of the patients.

Clinical features and circulating gonadotropin, insulin, and androgen interactions in women with polycystic ovarian disease

OBJECTIVE To investigate the interactions of hyperinsulinemia and inappropriate gonadotropin secretion in women with polycystic ovarian disease (PCOD). DESIGN Comparative study of endocrinologic parameters in subjects with PCOD. SETTING Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. PATIENTS Fourteen nonobese and 10 obese patients with PCOD. Seven healthy women for reference data collection. Normal thyroid function, serum prolactin concentration, normal diurnal cortisol variation, euglycemia in all subjects. MAIN OUTCOME MEASURES Serum concentrations of insulin, testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, immunoreactive luteinizing hormone (LH), bioactive LH, and follicle-stimulating hormone (FSH). RESULTS The concentration of insulin was higher and that of bioactive LH was lower in obese than in nonobese PCOD women in whom the levels were also above the upper reference value. There was a negative correlation between insulin and bioactive LH levels (r = -0.57). Bioactive LH correlated inversely with the body mass index (BMI) (r = -0.50). After eliminating the effect of the BMI, the correlation between bioactive LH and insulin was no longer significant (r = -0.37). The bioactive LH and immunoreactive LH/FSH ratio correlated significantly (r = 0.68). CONCLUSIONS These data demonstrate that hyperandrogenic women can be divided into two subgroups: those with insulin resistance, normal or minimally elevated LH, and markedly elevated insulin levels; and those with elevated LH levels, no insulin resistance, and normal insulin concentrations. Obesity is associated with the former, and high bioactive LH levels with the latter subgroup.