Type 2 diabetes mellitus in women with polycystic ovary syndrome during a 24-year period: importance of obesity and abdominal fat distribution.

STUDY QUESTION: What are the predictive factors for later development of type 2 diabetes (T2DM) in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Obesity and abdominal fat distribution in women with PCOS in the mid-fertile years were the major risk factors for T2DM development 24 years later when lifestyle factors were similar to controls. WHAT IS KNOWN ALREADY: Women with PCOS have an increased prevalence of T2DM. STUDY DESIGN SIZE DURATION: A longitudinal and cross-sectional study was performed. Women with PCOS were examined in 1992 and in 2016. Randomly selected, age-matched women from the general population served as controls. PARTICIPANTS/MATERIALS SETTING METHODS: Women with PCOS (n = 27), attending an outpatient clinical at a tertiary care centre for infertility or hirsutism were diagnosed in 1992 (mean age 30 years) and re-examined in 2016 (mean age 52 years). Women from the World Health Organization MONItoring of trends and determinants for CArdiovascular disease (WHO MONICA-GOT) 2008, aged 38-68 years, served as controls (n = 94), and they were previously examined in 1995. At both at baseline and at follow-up, women had blood samples taken, underwent a clinical examination and completed structured questionnaires, and the women with PCOS also underwent a glucose clamp test at baseline. MAIN RESULTS AND THE ROLE OF CHANCE: None of women with PCOS had T2DM at baseline. At the 24-year follow-up, 19% of women with PCOS had T2DM versus 1% of controls (P < 0.01). All women with PCOS who developed T2DM were obese and had waist-hip ratio (WHR) >0.85 at baseline. No difference was seen between women with PCOS and controls regarding use of high-fat diet, Mediterranean diet or amount of physical activity at follow-up at peri/postmenopausal age. However, women with PCOS had a lower usage of a high-sugar diet as compared to controls (P = 0.01). The mean increases in BMI and WHR per year were similar in women with PCOS and controls during the follow-up period. LIMITATIONS REASONS FOR CAUTION: The small sample size of women with PCOS and the fact that they were recruited due to infertility or hirsutism make generalization to women with milder forms of PCOS uncertain. WIDER IMPLICATIONS OF THE FINDINGS: Obesity and abdominal fat distribution, but not hyperandrogenism per se, in women with PCOS in the mid-fertile years were the major risk factors for T2DM development 24 years later when peri/postmenopausal. Lifestyle factors were similar to controls at that time. STUDY FUNDING/COMPETING INTERESTS: The study was financed by grants from the Swedish state under the agreement between the Swedish government and the country councils, the ALF-agreement (ALFGBG-718611), the Gothenburg Medical Association GLS 694291 and 780821, the Swedish Heart Lung Foundation and Hjalmar Svensson Foundation. The authors have no conflict of interest.

Caribbean yellow-band syndrome on Montastraea faveolata is not transmitted mechanically under field conditions.

Caribbean yellow-band syndrome is a highly prevalent coral disease whose transmission mechanisms are unknown. Affected corals often show multifocal lesions of yellow-colored tissue. We tested the hypothesis that a mechanical vector was responsible for these multifocal lesions. Four presumably non-resistant colonies were experimentally manipulated. Tissue and microbial assemblages were taken from diseased tissue and injected into healthy-looking tissue. Seawater injections were used as controls. The manipulations created a small wound, as would be generated by a coral predator. After 1 mo, all lesions healed and showed no signs of disease. We therefore reject the hypothesis that a mechanical vector, acting in a similar way as our manipulations, was responsible for the multifocal lesions.

Coral diversity and disease in Mexico.

Field studies and empirical tests of the 'diversity-disease hypothesis' demonstrate the effects of species richness on disease transmission and severity in plant systems. Yet the converse, i.e. effects of disease on diversity, is rarely considered in either relatively well-studied plant systems or marine ecosystems. We investigated these effects along the Mexican Yucatan Peninsula to (1) quantify the relationship between disease prevalence and coral diversity, (2) test the hypothesis that octocoral and scleractinian disease prevalence are associated with one another, and (3) establish a long-term dataset. Aspergillosis of sea fans and 6 scleractinian diseases were documented. Prevalence of aspergillosis declined from 12.85% in 2002 to 5.26% in 2004, while prevalence of scleractinian diseases remained relatively constant at 5.7 +/- 0.8% in 2002 and 7.96 +/- 0.7% in 2004. Sites were relatively rich (71 species of octocoral and scleractinian corals) and even (E5 > 0.5). Sea fan disease prevalence was not associated with scleractinian disease prevalence, nor were there consistent associations between disease and measures of diversity. However, the most abundant octocoral and scleractinian species are susceptible to infection with several diseases, and disease may alter coral diversity in complex ways. These data represent the first in what will become a long-term dataset monitoring disease prevalence and associated changes in coral diversity.

Necrotic patches affect Acropora palmata (Scleractinia: Acroporidae) in the Mexican Caribbean.

An outbreak of necrotic patches was observed affecting Acropora palmata in the Mexican Caribbean in the summer of 1999. This study documents the tissue loss produced by these patches. Following a marked initial increase in the number of patches, there was a decrease in the appearance of new patches but the size of the patches increased throughout the study. In some cases patches expanded but in most cases they enlarged due to fusion of 2 or more patches. Patches recovered but not sufficiently to overcome damage in most colonies surveyed. Percentage tissue loss does not appear to be directly related to temperature but may be related to a combination of factors associated with prolonged summer doldrum-like conditions. The necrotic patch syndrome can have a substantial impact in tissue loss in affected A. palmata colonies.

The disabilities of the arm, shoulder and hand (DASH) outcome questionnaire: reliability and validity of the Swedish version evaluated in 176 patients.

The disabilities of the arm, shoulder and hand (DASH) questionnaire is a self-administered region-specific outcome instrument developed to measure upper-extremity disability and symptoms. The DASH consists mainly of a 30-item disability/symptom scale. We performed cross-cultural adaptation of the DASH to Swedish, using a process that included double forward and backward translations, expert and lay review, as well as field-testing to achieve linguistic and conceptual equivalence. The Swedish version's reliability and validity were then evaluated in 176 patients with upper-extremity conditions. The patients completed the DASH and SF-12 generic health questionnaire before elective surgery or physical therapy. Internal consistency of the DASH was high (Cronbach alpha 0.96). Test-retest reliability, evaluated in a subgroup of 67 patients who completed the DASH on two occasions, with a median interval of 7 days, was excellent (intraclass correlation coefficient 0.92). Construct validity was shown by a positive correlation of DASH scores with the SF-12 scores (worse upper-extremity disability correlating with worse general health), stronger correlation with the SF-12 physical than with the mental health component, correlation of worse DASH scores with worse self-rated global health, and ability to discriminate among conditions known to differ in severity. The Swedish version of the DASH is a reliable and valid instrument that can provide a standardized measure of patient-centered outcomes in upper-extremity musculoskeletal conditions.

Effects of two antiandrogen treatments on hirsutism and insulin sensitivity in women with polycystic ovary syndrome.

Thirty-two women with polycystic ovary syndrome (PCOS) were allocated to two antiandrogen treatment regimens; 28 women completed the trial. Twenty women were treated with ethinyloestradiol and cyproterone acetate (EO-CA) cyclically for 6 months and eight women were treated with the gonadotrophin releasing hormone (GnRH) analogue, goserelin for 6 months. Effects on hirsutism, insulin sensitivity (estimated by glucose clamp technique), blood lipids and hormones were measured. Women treated with EO-CA showed a reduction in hirsutism (P <0.05), and decreased serum androgen concentrations (P <0.001) as well as reduced insulin sensitivity (P <0.05). In women treated with goserelin, serum androgen concentrations also decreased (P <0.001), but there was no significant reduction of hirsutism. This group, however, showed an improved insulin sensitivity (P <0.05) despite an unchanged body mass index. Bone mineral density was unaltered in both treatment groups. The reduction in androgen concentrations caused by EO-CA was not paralleled by increased insulin sensitivity, most probably due to the effect of ethinyloestradiol per se. In contrast, the reduction in androgen concentrations by goserelin was accompanied by an improved insulin sensitivity.

In vitro production of cyclic AMP and steroids from an ovarian Sertoli-Leydig cell tumor. Notes on clinical management.

A 27 year old nulliparous woman with a history of chronic anovulation and signs of virilization with a markedly elevated serum level of testosterone, underwent a laparotomy with peroperative bilateral ovarian vein catheterization and bilateral bisection of both ovaries. A solid, 1.5 cm, well delimited tumor located centrally in the right ovary, was excised. Testosterone levels in ovarian venous blood from the tumor bearing side, were 88.4 nmol/l and from the contralateral ovary 3.9 nmol/l. Histopathological examination showed a Sertoli-Leydig cell tumor which was radically extirpated. Postoperatively, the serum levels of androgen normalized, the woman had regular cycles, became pregnant and delivered a normal female baby. Pieces of tumor tissue were incubated for 2 h, with and without addition of gonadotropins and adrenocorticotropic hormone (ACTH). Human chorionic gonadotropin (CG), follicle stimulating hormone (FSH) and adrenocorticotropic hormone (ACTH) caused significant increases in cyclic monophosphate (cAMP) production in tumor tissue in vitro, as compared to controls. Furthermore, ACTH also significantly stimulated 17 beta-estradiol production. In tumor cells cultured for 48 h, FSH slightly, but not significantly, increased the production of progesterone. In the cell culture, [3H]-thymidine incorporation into deoxyribonucleic acid (DNA) was stimulated by IGF1 alpha but not by hCG and FSH. It is concluded that Sertoli-Leydig cell tumors may be sensitive to gonadotropins and ACTH and that their small size, solid shape and intra-ovarian localization can cause diagnostic difficulties.

Hemostatic and metabolic variables in women with polycystic ovary syndrome.

OBJECTIVE: To study whether a previously demonstrated increased morbidity in cardiovascular disease (CVD) and diabetes mellitus in women with polycystic ovary syndrome (PCOS) is associated with certain hemostatic variables that are known to be markers for CVD. DESIGN: The study was a trans-sectional follow-up study from a cohort of women with PCOS. SETTING: The women with PCOS were recruited from hospital clinics and referents were randomized from a population study of women from the same area. PARTICIPANTS: The investigation involved 28 women aged 43 to 62 years diagnosed to have PCOS on ovarian histopathology at wedge resection 25 to 34 years previously and 56 referents who were matched by age and body mass index. MAIN OUTCOME MEASURES: In connection with a clinical investigation, the hemostatic variables fibrinogen, von Willebrand factor antigen, factor VII procoagulant activity, factor VII antigen, and plasminogen activator inhibitor as well as the metabolic variables serum insulin and serum triglycerides were assayed. RESULTS: There was a strong positive correlation between serum concentrations of triglyceride, basal insulin, and abdominal obesity on the one hand, and plasminogen activator inhibitor, fibrinogen, and von Willebrand factor on the other, among women with PCOS as well as among referents. There were significantly higher mean concentrations of fibrinogen and factor VII:Ag among referents, but the mean values of most hemostatic variables studied showed no differences between the groups. CONCLUSION: Women with an altered metabolic profile were also found to have affected hemostatic factors, but PCOS in itself did not seem to influence them.

Polycystic ovary syndrome and risk for myocardial infarction. Evaluated from a risk factor model based on a prospective population study of women.

In order to estimate whether women with polycystic ovary syndrome (PCOS) have an increased risk of developing myocardial infarction, a risk factor model was applied on 33 women with PCOS and 132 age matched referents. The risk factor model was established from independent risk factors for myocardial infarction in a prospective population study of 1462 women in Göteborg, Sweden. The independent risk factors were age, manifest hypertension, manifest diabetes mellitus, central obesity measured as increased waist to hip circumference ratio and serum triglyceride concentration. A considerably increased risk (relative risk of 7.4) of developing myocardial infarction was observed for women with PCOS compared to age-matched referents. Since the risk factors include variables correlated to obesity, the results indicate that advice on dietary restriction is an important part of the treatment once the diagnosis is established.

Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating hormones.

OBJECTIVE: To determine if the hormonal imbalance in women with polycystic ovary syndrome (PCOS) continues into and after menopause and to analyze factors constituting an increased risk for developing metabolic disorders. DESIGN: The study was a transectional retrospective cohort follow-up of patients with PCOS. SETTING: The women with PCOS were recruited from hospital clinics, and referents were randomized from a population study of women. PARTICIPANTS: Thirty-three women ages 40 to 59 years with ovarian histopathology typical of PCOS at wedge resection 22 to 31 years previously; 132 age-matched referents were analyzed. MAIN OUTCOME MEASURES: Clinical data were collected via a questionnaire supplemented with an interview in connection to a clinical examination that also included fasting venous sampling. RESULTS: Infertility, hirsutism, and oligomenorrhea were more common among the subjects with PCOS, but there was a considerable spontaneous restitution of cyclic regularity with time. Women with PCOS were more often hysterectomized and entered menopause later compared with referents. The hormone data show a typical profile for PCOS. Compared with referents women with PCOS showed marked increase in prevalence of central obesity, higher basal serum insulin concentrations, and a higher prevalence of diabetes mellitus and hypertension. CONCLUSION: Perimenopausal women with PCOS have an increased morbidity in hypertension and diabetes mellitus that adds to the classic symptoms, such as anovulation, hirsutism, and infertility.

Endometrial carcinoma; ovarian dysfunction--a risk factor in young women.

From a referral area comprising one-fifth of the Swedish female population we investigated possible risk factors for endometrial cancer (EC) in different age groups. Seventy-seven women aged 31-45 with EC were collected retrospectively, and 99 women aged 46-65 were consecutively collected. Both groups were compared to referents randomly selected from a population based study from the city of Göteborg. The referents consisted of 1746 women aged 39-65 years. All cases were studied by hospital record and 82% of the women aged 31-45 years and 85% of those aged 46-65 years were studied by an extensive questionnaire. Among the referents 1409 (81%) were investigated by the above-mentioned questionnaire. Hirsutism, increased body mass index (BMI) and hypertension were significantly more common in both EC groups compared to referents. Nulliparity and infertility were significantly more common in the young EC group. Referents used combined oral contraceptives significantly more often than women developing EC. There was, however, no difference between the groups with respect to the duration of medication with combined oral contraceptives. There was a significant negative correlation between cigarette smoking and the development of EC. These findings indicate that untreated ovarian dysfunction like that present in polycystic ovarian disease (PCO) with unopposed estrogen action on the endometrium is associated with EC in younger women, and that smoking may protect against EC by an 'anti-estrogenic' effect.

A model for prediction of endometrial cancer.

An epidemiological statistical model was designed to identify women at low and high risk of developing endometrial cancer (EC). The model was based on a number of easily identified clinical factors such as hirsutism, parity, diabetes mellitus, body mass index (BMI) and smoking. A retrospectively collected series of 77 women aged 31 to 45 years with EC and a prospectively collected series of 122 women aged 43 to 70 years with EC were compared with 1409 controls. The participation frequencies in the two case materials were 83 and 87%, respectively. The series were examined by means of a questionnaire. In a stepwise multiple logistic regression analysis of the entire series the following variables were found to be significant; hirsutism, parity, BMI, diabetes mellitus and smoking.

Fatal arsenic poisoning--a case report.

A worker was buried under arsenic trioxide in an industrial accident. He was almost immediately released but had inhaled and swallowed substantial amounts of arsenic dust. In spite of intensive treatment, circulatory collapse could not be prevented, and he died 6 h after the exposure. The treatment, autopsy findings, and arsenic concentrations in tissues and body fluids are described and discussed.

Oral replacement with estradiol-cyclooctyl acetate: a new estradiol analogue. Effects on serum lipids, proteins, gonadotrophins, estrogens and uterine endometrial morphology.

Estradiol-cyclooctyl acetate (E2CoA) dissolved in arachis oil was given orally at a dose of 0.5 mg/day for 21 days to 11 oophorectomized women. The study was performed in two steps. In the first step the effects of E2CoA, administered after an overnight fast, on plasma estrone, estradiol, FSH, LH, prolactin as well as on serum proteins, fatty acids, oral glucose tolerance test and on the cervical and endometrial morphology were compared to the effects of daily oral intake of 25 micrograms ethinyl estradiol (EE) in a cross-over study. In the second step the effects of E2CoA in nonfasting conditions on plasma estrone, estradiol, FSH and LH were studied. E2CoA alleviated climacteric estrogen-deficiency symptoms in all women. It showed an estrogenic effect on cervical and endometrial morphology and depressed FSH, though more weakly than EE. No side effects were seen. The unchanged metabolic parameters after 21 days of E2CoA treatment may support the assumption of a weak estrogenic effect, but the relatively slow resorption and relatively low estradiol/estrone ratio found in this study do not confirm the hypothesis that the drug is resorbed by the chylomicrones. Further investigation on the resorption of E2CoA in nonfasting women is, however, needed.

Effect of oestriol, oestradiol valerate and ethinyloestradiol on serum proteins in oestrogen-deficient women.

The effect of oestriol (3 mg for 3 mth), oestradiol valerate (2 mg for 3 mth) and ethinyloestradiol (0.025 mg for 21 days) on sex hormone binding globulin (SHBG), transcortin, ceruloplasmin and pregnancy-associated macro-globulin (PAG) was analysed in oestrogen-deficient women. The doses of oestrogens were therapeutically effective for the treatment of oestrogen-deficiency symptoms. Treatment with 0.025 mg ethinyloestradiol induced a 281% increase in PAG, a 119% increase in SHBG, a 74% increase in transcortin and a 74% increase in ceruloplasmin levels. Administration of 2 mg oestradiol valerate resulted in a 40% increase in SHBG, a small increase in transcortin and ceruloplasmin, whereas PAG levels remained unaffected. None of the parameters tested were affected by oestriol treatment. PAG was clearly the most sensitive parameter for ethinyloestradiol while SHBG was the most sensitive parameter for oestradiol valerate. These results show no relationship between clinical efficacy and effect of plasma protein synthesis, and demonstrate that one has to be very careful when comparing potency estimates for different oestrogens and different parameters.

A study of chromosomal aberrations in miners exposed to diesel exhausts.

A study was made of chromosome aberrations in cultured lymphocytes from a group of 14 miners exposed to diesel exhausts and a reference group of office employees and construction workers. No increased frequency of chromosomal aberrations was observed. The frequency of chromosomal aberrations (both gaps and breaks) was, however, found to be associated with smoking.

Arsenic exposure and mortality: a case-referent study from a Swedish copper smelter.

An increased mortality from lung cancer, cardiovascular disease, haematolymphatic malignancy and cirrhosis of the liver has been reported among smelter workers and others exposed to arsenic. This study uses the case-referent (case-control) technique and is concerned with workers in a copper smelter in a complex work environment, characterised by the presence of trivalent arsenic in combination with sulphur dioxide and copper, and also with other agents. Lung cancer mortality was found to be increased about five-fold and cardiovascular disease about two-fold, showing a dose-response relationship to arsenic exposure. Mortality from malignant blood disease (leukaemia and myeloma) and cirrhosis of the liver was also slightly increased. This mortality pattern among the smelter workers is consistent with earlier reports. An increased mortality from cardiovascular disease in this type of industry is of particular interest as it has been reported only once before.