Göran Lindstedt

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.

Serum insulin‐like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin

OBJECTIVE There Is a cllnlcal need for population based reference values for serum Insulin‐like growth factor I (IGF‐I). We have therefore determined serum IGF‐i concentrations In a random population sample from Sweden and have related the levels to age, sex, llfe style factors, blood pressure, body composition, blood llplds, plasma fibrlnogen, Parathyroid hormone (PTH) and osteocalcin.

A DOUBLE-BLIND CROSS-OVER 12-MONTH STUDY OF l-THYROXINE TREATMENT OF WOMEN WITH ‘SUBCLINICAL’ HYPOTHYROIDISM

Twenty women, who had been randomly selected from women with subclinical hypothyroidism identified in a population study were treated with l‐thyroxine and placebo in a double‐blind cross‐over design during 2·6 months. Three women did not complete the study, one because she moved to another part of the country, and two because of nervousness and sense of tachycardia. None of these ‘drop‐outs’ had any objective signs of overtreatment; they had normal pulse rate and a serum T3 concentration within the reference interval. During l‐thyroxine treatment serum procollagen‐III‐peptide concentration increased in 13 women out of the 17 women completing the study and at the end of treatment the mean concentration was significantly raised (P>0·001). Serum concentrations of procollagen‐III‐peptide then correlated with those of free thyroxine (P>0·01), total thyroxine (P>0·05), and reverse triiodothyronine (P>0·05). The same comparison revealed little or no effect on the concentrations of serum creatine kinase activity, transcortin or sex‐hormone binding globulin. Heart rate‐corrected preejection period and symptom score decreased (P>0·05). Four women starting with l‐thyroxine showed a marked and prolonged (4–6 months) rise in thyrotrophin concentration during the subsequent placebo period, but remained clinically euthyroid. Four women (of 17) improved during therapy as judged by psychometric testing and their own rating. We could not by pretreatment observations identify these four women apart from serum free and total 3,5,3′‐triiodothyronine concentrations in the lower part of the health‐associated reference interval. Subclinical hypothyroidism is common among middle‐aged and old women, and our findings indicate that approximately one woman in four with this ‘subclinical’ condition will benefit from L‐thyroxine treatment.

Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency

OBJECTIVE Growth hormone deficiency in adults with hypopituitarism has previously received little attention. Recent data, however, suggest that GH deflciency might be essential for the long‐term prognosis of these patients. Earlier studies have documented that GH regulates body composition; in this, body composition in adult patients with hypopituitarism including GH deficiency was studied. DESIGN A follow‐up study of patients with hypopituitarism on routine replacement therapy with l‐thyroxine, cortisone acetate and sex steroids.

Low Sex-Hormone-Binding Globulin Concentration as Independent Risk Factor for Development of NIDDM: 12-Yr Follow-Up of Population Study of Women in Gothenburg, Sweden

Serum sex-hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) concentrations were evaluated as risk factors for the development of non-insulin-dependent diabetes mellitus (NIDDM), myocardial infarction, stroke, and premature death in a prospective study of 1462 randomly selected women, aged 38–60 yr, over 12 yr of observation. In multivariate analysis, taking only age into consideration as a confounding factor, low initial concentration of SHBG was significantly correlated to the incidence of NIDDM and stroke, and high initial concentration of CBG was correlated to the incidence of NIDDM. There were also significant correlations between SHBG and CBG concentrations on one hand and possible risk factors for the end points studied, such as serum triglycerides, serum cholesterol, fasting blood glucose, body mass, body mass index, waist/hip ratio, smoking habits, and systolic blood pressure, on the other. When these possible confounders, in addition to age, were taken into consideration in multivariate analyses, only the inverse significant correlation between SHBG and NIDDM remained. The increased incidence of diabetes was confined to the lowest quintile of SHBG values, where it was 5-fold higher than in the remaining group. This incidence was further increased to 8- and 11-fold in the lowest 10 and 5% of the values, respectively. We conclude that SHBG is a uniquely strong independent risk factor for the development of NIDDM in women.

Screening for iron deficiency: an analysis based on bone‐marrow examinations and serum ferritin determinations in a population sample of women

Summary Efficacy of different methods in screening for iron deficiency was re‐examined in a randomly selected sample of 38‐year‐old women (n= 203) with known iron status based on absence/presence of stainable iron in bone‐marrow smears. The study was made in 1968–69. Serum ferritin (SF) was determined in 1978 in frozen sera using the Kamco IRMA and, in 1992, samples were re‐analysed using a RIA calibrated with the International Standard 80/602 for SF determination. The effect of storage on SF was calculated from a previously established relationship (courtesy of Dr Mark Worwood. Cardiff) between the results obtained with the Ramco assay and assays calibrated with IS 80/602. The distributions in iron replete and iron deficient women showed less overlap (diagnostic efficiency 91%) for SF than for other haematological parameters. The best discrimination was obtained at SF<16 μg/l (specificity 98%: sensitivity 75%). Absence of iron stores was associated with signs of an iron deficient erythropoiesis. starting already at SF 25–40 μg/l. Use of multiple criteria to diagnose iron deficiency falsely reduces prevalence figures for iron deficiency.

Follitropin (FSH) Deficiency in an Infertile Male due to FSHβ Gene Mutation. A Syndrome of Normal Puberty and Virilization but Under-developed Testicles with Azoospermia, Low FSH but High Lutropin and Normal Serum Testosterone Concentrations

Abstract We studied a man who sought medical attention at age 28 years because of infertility in both his first and second marriages. His sexual development appeared to have been normal, with normal puberty and virilization, and normal libido and sexual potency. At examination, his testicles were small and soft; otherwise he had a normal physical appearance. Evaluations revealed azoospermia, undetectable in serum before and after 100 μg of intravenously administered gonadotrophin releasing hormone, but moderately elevated lutropin concentration with a brisk rise after gonadotrophin releasing hormone. The α subunit concentration was normal before and after gonadotrophin releasing hormone; that of inhibin B was very low. Analysis of the follitropin β gene, exon 3, revealed a Cys82 → Arg mutation (TGT → CGT). Judging from studies of the biosynthesis of the chorionic gonadotrophin β subunit one may conclude that inability to form the first intramolecular disulphide bond in the follitropin β subunit results in an abnormal tertiary structure during follitropin β biosynthesis with extensive intracellular degradation of the products, inability to associate with the α subunit and defective glycosylation, as well as inability to form a biologically active hormone. This first male case of follitropin deficiency thus defines a new syndrome of male infertility.

Effects of electro-acupuncture on anovulation in women with polycystic ovary syndrome

Background. The present study was designed to evaluate if electro‐acupuncture (EA) could affect oligo‐/anovulation and related endocrine and neuroendocrine parameters in women with polycystic ovary syndrome (PCOS).

The Pituitary-Gonadal Axis and Health in Elderly Men: A Study of Men Born in 1913

The results of recent studies suggest that a relative hypogonadism in men is associated with several established risk factors for prevalent diseases. Therefore, we determined total and free testosterone, luteinizing hormone (LH), and sex-hormone binding globulin (SHBG) in a cohort of randomly selected men (n = 659) at 67 years of age. These data were analyzed cross-sectionally in relation to blood glucose and serum insulin, which were measured while fasting and after an oral glucose tolerance test, in addition to plasma lipids and blood pressure. The data were also analyzed in relation to impaired glucose tolerance (IGT) and diabetes, which were discovered at examination or earlier diagnosis. Risk factors for the development of diabetes up to 80 years of age were analyzed with univariate and multivariate statistics. Total and free testosterone and SHBG concentrations correlated negatively with glucose and insulin values; total testosterone and SHBG, with triglycerides; and SHBG, with blood pressure (from P < 0.05 to P < 0.01). Men with IGT or newly diagnosed diabetes had higher BMI values (26.2 ± 0.31 and 27.0 ± 0.59 [mean ± SE], respectively) and waist circumference (99.0 ± 1.03 and 100.5 ± 1.57) than nondiabetic men (BMI, 25.1 ± 0.14; waist circumference, 95.4 ± 0.47; P < 0.05), indicating abdominal obesity. Such men and men with previously diagnosed diabetes had, in general, lower total and free testosterone and SHBG levels, while those for LH were not different. In multivariate analyses that included BMI, waist-to-hip ratio, total and free testosterone, and SHBG, the remaining independent predictors for the development of diabetes were low total testosterone (P = 0.015) and, on the borderline, low SHBG (P = 0.053). In relation to nondiabetic men, the risk ratio for mortality, myocardial infarction, and stroke increased gradually and significantly from 1.18 to 1.68, from 1.51 to 1.78, and from 1.72 to 2.46 in men with IGT, newly diagnosed diabetes, and previously known diabetes, respectively. It was concluded that low testosterone and SHBG concentrations in elderly men are associated with established risk factors for diabetes and in established diabetes. Moreover, low testosterone levels independently predict the risk of developing diabetes. In different degrees of expression, the diabetic state predicts strongly (and gradually mortality from) myocardial infarction and stroke. It has been suggested that a relative hypogonadism might be a primary event, because other studies have shown that testosterone deficiency is followed by insulin resistance, which is ameliorated by testosterone substitution. The data suggest that the relative hypogonadism involved might be of both central and peripheral origin.

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.