Kristiina Ruutiainen

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.

Polycystic ovaries in women with gestational diabetes.

Objective To examine the occurrence of polycystic ovaries (PCO) in women with gestational diabetes mellitus (GDM). Methods This was a retrospective comparative study of ultrasonographic findings of ovaries in 31 women with GDMand 30 healthy controls matched according to maternal age and body mass index (BMI). Women who presented evidence of impaired glucose tolerance during pregnancy were excluded from the control group. Transvaginal ultra-sonographic examination was performed during the follicu-lar phase of the menstrual cycle, after breast-feeding had been discontinued. Results Polycystic ovary was a more frequent finding among women with GDM than among controls: 14 women with GDM (44%) and two controls exhibited PCO. No differences were found in BMI before pregnancy or in the weight gain during pregnancy between the groups. No difference was observed in the mean birth weight of the infants between the study groups. Conclusion Polycystic ovaries were a common finding among women with GDM. The data suggest that women with PCO are at risk for developing GDM and should be screened accordingly.

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.

Influence of body mass index and age on the grade of hair growth in hirsute women of reproductive ages

The relationships between the hair growth in different body regions, body mass index (BMI) and age were studied in 225 women of reproductive ages referred for hirsutism. The regularity of the cycles was registered, and 109 of the patients were interviewed for their maximum weight, teenage obesity, and age of menarche. The serum androgens were measured in the follicular phase. The results indicate that facial hirsutism is associated with BMI (rho = 0.41, P less than 0.001) independently of age and the testosterone (T) to sex hormone-binding globulin (SHBG) ratio. Facial hirsutism is also correlated with age (rho = 0.37, P less than 0.001) irrespective of BMI (rho = 0.26, P less than 0.001) or the T/SHBG ratio (rho = 0.43, P less than 0.001). In contrast, the hair growth on trunk area is related to the T/SHBG ratio (rho = 0.35, P less than 0.001) but not to BMI or age when the correlations are adjusted for the grade of hyperandrogenemia. The women with severe facial hirsutism had a higher maximum weight (P less than 0.001) and more teenage obesity (P less than 0.01) than other hirsute patients. They also had a slightly earlier menarche compared with their agemates than the women with mild or absent facial hair (P less than 0.05). The data suggest differences in the regulation of hair growth between the face and trunk areas.

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.

The grade of hirsutism correlated to serum androgen levels and hormonal indices

Abstract. The degree of hair growth of 64 hirsute women was clinically graded. The patients were divided into two groups with respect to the ratio between the serum luteinizing hormone (LH) and the follicle‐stimulating hormone (FSH). The two groups did not differ in terms of the grade of hirsutism, serum testosterone (T), calculated free testosterone (FTc), androstenedione (A), dehydroepiandrosterone sulphate (DHEAS), sex hormone binding globulin (SHBG), estradiol, or cortisol levels. In patients with a LH/FSH ratio of 3.0 or less (n = 49), FTc and A correlated well (ϱ 0.49, p < 0.001) to the clinically graded hormonal hirsutism score, while SHBG showed an inverse correlation to it. By contrast, no correlations were found in patients with a serum LH/FSH ratio exceeding 3.0 (n = 15). Various indices for hyperandrogenism were calculated. In patients with lower LH/FSH ratio, T/SHBG, T/SHBG + A/100 and T/SHBG + A/100 +DHEAS/100 showed the best correlation with the clinically scored hair growth. These results show that correlations between hirsutism and hyperandrogenism can be demonstrated.

Hirsutism: Definitions and Etiology

Hirsutism as a sign of hyperandrogenism is a common endocrinological disorder in women. Its spectrum varies from mild forms with dominating psychic component to severe forms associated with virilization. The severity should be assessed by semiobjective scoring systems, the use of which also allows the systematic follow-up of the results of treatment. An increase in serum androgen levels or an increased turnover of androgens can be detected in most patients. Enhanced peripheral conversion of androgens to locally acting androgen also leads to hirsutism. The thorough investigation of the endocrinological milieu is required to rule out androgen producing neoplasms. In most patient, however, disturbances are functional, among which polycystic ovary syndrome is the commonest. It is a disorder exhibiting a complexity of changes in endocrinological interactions. Besides inappropriate gonadotropin secretion insulin and insulin like growth factor are also involved. The opioidergic system also seems to be affected. Polycystic ovary syndrome is also associated with obesity and infertility, both of which require attention.

Serum testosterone, androstenedione and luteinizing hormone levels after short‐term medroxyprogesterone acetate treatment in women with polycystic ovarian disease

Background. Medroxyprogesterone acetate (MPA) ‐treatment suppresses serum gonadotropin and androgen concentrations in women with polycystic ovarian disease (PCOD). This study ws designed to determine serum testosterone (T), androstenedione (A) and luteinizing hormone (LH) patterns in a group of oligomenorrheic PCOD patients after MPA‐treatment.

Androgen parameters in hirsute women: Correlations with body mass index and age

The recent work was designed for studying the effects of body mass index (BMI) and age on serum hormone values in hirsute women of reproductive years with nontumorous hyperandrogenism. Two hundred patients were studied in the follicular phase of the cycle. The serum levels of testosterone (T), androstenedione (A), or dehydroepiandrosterone sulfate (DHEAS) were not associated with BMI, whereas the T/sex hormone-binding globulin (T/SHBG) ratio was significantly correlated with BMI independently of the effect of age. All serum androgens were significantly negatively correlated with age, and the serum levels were significantly lower in women older than 41 years when compared with women aged 25 years or less. After correcting for the effect of BMI, there was also a negative correlation between the T/SHBG ratio and age. The correlations between serum androgen parameters were calculated. We conclude that already in reproductive years, the age of the patient has modulating effects on serum androgens, and it should be taken into account when studying the hormone profile of hirsute women.

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.