| 1. |
- Eriksson, Anna-Lena, 1971, et al.
(författare)
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SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density.
- 2006
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:12, s. 5029-37
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: SHBG regulates free sex steroid levels, which in turn regulate skeletal homeostasis. Twin studies have demonstrated that genetic factors largely account for interindividual variation in SHBG levels. Glucuronidated androgen metabolites have been proposed as markers of androgenic activity. OBJECTIVE: Our objective was to investigate whether polymorphisms in the SHBG gene promoter [(TAAAA)(n) microsatellite and rs1799941 single-nucleotide polymorphism] are associated with serum levels of SHBG, sex steroids, or bone mineral density (BMD) in men. DESIGN AND STUDY SUBJECTS: We conducted a population-based study of two cohorts of Swedish men: elderly men (MrOS Sweden; n congruent with 3000; average age, 75.4 yr) and young adult men (GOOD study; n = 1068; average age, 18.9 yr). MAIN OUTCOME MEASURES: We measured serum levels of SHBG, testosterone, estradiol, dihydrotestosterone, 5alpha-androstane-3alpha,17beta-diol glucuronides, androsterone glucuronide, and BMD determined by dual-energy x-ray absorptiometry. RESULTS: In both cohorts, (TAAAA)(n) and rs1799941 genotypes were associated with serum levels of SHBG (P < 0.001), dihydrotestosterone (P < 0.05), and 5alpha-androstane-3alpha,17beta-diol glucuronides (P < 0.05). In the elderly men, they were also associated with testosterone and BMD at all hip bone sites. The genotype associated with high levels of SHBG was also associated with high BMD. Interestingly, male mice overexpressing human SHBG had increased cortical bone mineral content in the femur, suggesting that elevated SHBG levels may cause increased bone mass. CONCLUSIONS: Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men.
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| 2. |
- Jedel, Elizabeth, 1962, et al.
(författare)
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Impact of electroacupuncture and exercise on hyperandrogenism and oligo/amenorrhoea in women with polycystic ovary syndrome: A randomized controlled trial.
- 2011
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Ingår i: American Journal of Physiology - Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 300:1, s. E37-45
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Tidskriftsartikel (refereegranskat)abstract
- Background: Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism, oligo/amenorrhea, and polycystic ovaries. We aimed to determine whether low-frequency electro-acupuncture (EA) decreases hyperandrogenism and improves oligo/amenorrhea more effectively than physical exercise or no intervention. Methods: We randomized 84 women with PCOS, aged 18-37 years, to 16 weeks of low-frequency EA, physical exercise, or no intervention. The primary outcome measure-changes in the concentration of total testosterone (T) at week 16 determined by gas and liquid chromatography/mass spectrometry-was analyzed by intention-to treat. Secondary outcome measures were changes in menstrual frequency; concentrations of androgens, estrogens, androgen precursors, glucuronidated androgen metabolites; and acne and hirsutism. Outcomes were assessed at baseline, after 16 weeks of intervention, and after a 16-week follow-up. Results: After 16 weeks of intervention, circulating T decreased by -25%, androsterone glucuronide by -30%, and androstane-3α, 17β-diol-3glucuronide by -28% in the EA group (P=0.038, 0.030, and 0.047, respectively vs. exercise); menstrual frequency increased to 0.69/month from 0.28 at baseline in the EA group (P=0.018 vs. exercise). After the 16-week follow-up, the acne score decreased by -32% in the EA group (P=0.006 vs. exercise). Both EA and exercise improved menstrual frequency and decreased the levels of several sex steroids at week 16 and at the 16-week follow-up, compared to no intervention. Conclusion/Significance: Low-frequency EA and physical exercise improved hyperandrogenism and menstrual frequency more effectively than no intervention in women with PCOS. Low-frequency EA was superior to physical exercise and may be useful for treating hyperandrogenism and oligo/amenorrhea.
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| 3. |
- Jedel, Elizabeth, 1962, et al.
(författare)
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Sex steroids, insulin sensitivity and sympathetic nerve activity in relation to affective symptoms in women with polycystic ovary syndrome.
- 2011
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 36:10, s. 1470-9
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Affective symptoms are poorly understood in polycystic ovary syndrome (PCOS). Clinical signs of hyperandrogenism and high serum androgens are key features in PCOS, and women with PCOS are more likely to be overweight or obese, as well as insulin resistant. Further, PCOS is associated with high sympathetic nerve activity. OBJECTIVE: To elucidate if self-reported hirsutism, body mass index (BMI) and waistline, circulating sex steroids, sex hormone-binding globulin (SHBG), insulin sensitivity and sympathetic nerve activity are associated with depression and anxiety-related symptoms in women with PCOS. DESIGN AND METHODS: Seventy-two women with PCOS, aged 21-37 years, were recruited from the community. Hirsutism was self-reported using the Ferriman-Gallway score. Serum estrogens, sex steroid precursors, androgens and glucuronidated androgen metabolites were analyzed by gas and liquid chromatography/mass spectroscopy (GC-MS/LC-MS/MS) and SHBG by chemiluminiscent microparticle immunoassay (CMIA). Insulin sensitivity was measured with euglycemic hyperinsulinemic clamp. Sympathetic nerve activity was measured with microneurography. Symptoms of depression and anxiety were self-reported using the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Brief Scale for Anxiety (BSA-S). RESULTS: Circulating concentrations of testosterone (T) (P=0.026), free T (FT) (P=0.025), and androstane-3α 17β-diol-3glucuronide (3G) (P=0.029) were lower in women with depression symptoms of potential clinical relevance (MADR-S≥11). The odds of having a MADRS-S score ≥11 were higher with lower FT and 3G. No associations with BSA-S were noted. CONCLUSION: Lower circulating FT and 3G were associated with worse self-reported depression symptoms. The relationship between mental health, sex steroids and corresponding metabolites in PCOS requires further investigation.
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| 4. |
- Johannesson, Magnus, et al.
(författare)
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Combined Oral Contraceptives and Sexual Function in Women-a Double-Blind, Randomized, Placebo-Controlled Trial
- 2016
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press (OUP): Policy B - Oxford Open Option A. - 0021-972X .- 1945-7197. ; 101:11, s. 4046-4053
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Tidskriftsartikel (refereegranskat)abstract
- Context: There is a lack of knowledge about how oral contraceptives may affect sexual function.Objective: To determine whether there is a causal effect of oral contraceptives on sexuality. We hypothesized that a widely used pill impairs sexuality.Design: A double-blind, randomized, placebo-controlled trial. Enrollment began in February 2012 and was completed in August 2015.Setting: Karolinska University Hospital, Stockholm, Sweden.Participants: A total of 340 healthy women, aged 18-35 years, were randomized to treatment, and 332 completed the study.Interventions: A combined oral contraceptive (150 mu g levonorgestrel and 30 mu g ethinylestradiol) or placebo for 3 months of treatment.Main Outcome Measures: The primary outcome was the aggregate score on the Profile of Female Sexual Function (PFSF). Secondary outcomes were the seven domains of the PFSF, the Sexual Activity Log, and the Personal Distress Scale.Results: Overall sexual function was similar in women in the oral contraceptive and placebo groups. The PFSF domains desire (-4.4; 95% confidence interval [CI], -8.49 to -0.38; P =.032), arousal (-5.1; 95% CI, -9.63 to -0.48; P=.030), and pleasure (-5.1; 95% CI, -9.97 to -0.32; P =.036) were significantly reduced in comparison to placebo, whereas orgasm, concern, responsiveness, and self-image were similar between groups. The mean frequency of satisfying sexual episodes and personal distress were also similar between groups.Conclusions: This study shows no negative impact of a levonorgestrel-containing oral contraceptive on overall sexual function, although three of seven sexual function domains were adversely affected.
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| 5. |
- Swanson, Charlotte, 1975, et al.
(författare)
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Sex steroid levels and cortical bone size in young men are associated with a uridine diphosphate glucuronosyltransferase 2B7 polymorphism (H268Y).
- 2007
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:9, s. 3697-704
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Sex steroids are involved in the regulation of pubertal cortical bone expansion in males. In vitro studies have indicated that the enzyme uridine diphosphate glucuronosyltransferase (UGT) 2B7 has the capacity to glucuronidate sex steroids and their metabolites. OBJECTIVE: Our objective was to determine the impact of the H(268)Y polymorphism in the UGT2B7 gene on interindividual variation of serum levels of sex steroids and cortical bone dimensions. PARTICIPANTS: The population-based cohort Gothenburg Osteoporosis and Obesity Determinants study consists of 1068 young adult Swedish men (age 18.9 yr). MAIN OUTCOME MEASURES: Serum levels of sex steroids and the three major glucuronidated androgen metabolites, androstane-3alpha,17beta-diol-17glucuronide, androstane-3alpha,17beta-diol-3glucuronide, and androsterone-glucuronide, were analyzed. Cortical and trabecular volumetric bone mineral density and cortical bone size were measured by peripheral quantitative computer tomography. RESULTS: Serum levels of testosterone (YY 9% over HH; P < 0.01), dihydrotestosterone (YY 10% over HH; P < 0.01), and estradiol (YY 8% over HH; P < 0.01) were associated with the UGT2B7 H(268)Y polymorphism. The polymorphism was associated with androstane-3alpha,17beta-diol-17glucuronide and androstane-3alpha,17beta-diol-3glucuronide (P < 0.01), but not with androsterone-glucuronide serum levels. In addition, the UGT2B7 H(268)Y polymorphism was an independent predictor of cortical bone size, reflected by periosteal circumference and cortical moment of inertia (P < 0.01), in both the weight-bearing tibia and nonweight-bearing radius. CONCLUSIONS: The UGT2B7 H(268)Y polymorphism is independently associated with cortical bone size and serum sex steroid levels in young adult men. Subjects homozygous for the Y allele had higher serum testosterone and larger cortical bone size than subjects homozygous for the H allele. However, the underlying mechanism behind these associations is unknown and has to be studied further.
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| 6. |
- Swanson, Charlotte, 1975, et al.
(författare)
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The UDP Glucuronosyltransferase 2B15 D85Y and 2B17 Deletion Polymorphisms Predict the Glucuronidation Pattern of Androgens and Fat Mass in Men.
- 2007
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Ingår i: Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:12, s. 4878-82
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Tidskriftsartikel (refereegranskat)abstract
- Context: Previous in vitro studies have demonstrated that the UDP glucuronosyltransferase (UGT) 2B15 and UGT2B17 glucuronidate androgens and their metabolites. Objective: To determine in vivo if the UGT2B15 D(85)Y and the UGT2B17 deletion polymorphisms predict androgen glucuronidation and body composition. Participants: Two population-based cohorts including young adult (n=1068, age=18.9 years) and elderly (n=1001, age=75.3 years) men. Main Outcome Measures: Serum and urine levels of testosterone (T) and dihydrotestosterone (DHT) measured by GC-MS and serum levels of the major glucuronidated androgen metabolites androstane-3alpha,17beta-diol(androstanediol)-3glucuronide, androstanediol-17glucuronide and androsterone-glucuronide measured by LC-MS/MS. Body composition measured by DXA. Results: Both the UGT2B15 D(85)Y and the UGT2B17 deletion polymorphisms were associated with serum levels of androstanediol-17glucuronide (p<0.001) but not with levels of androstanediol-3glucuronide or androsterone-glucuronide in both cohorts. Glucuronidation of T and DHT was associated with the UGT2B17 deletion but not with the UGT2B15 D(85)Y polymorphism, suggested by strong associations between the deletion polymorphism and urine levels of these two hormones. Both polymorphisms were associated with several different measures of fat mass (p<0.01). The UGT2B17 deletion polymorphism was associated with insulin sensitivity (p<0.05) as indicated by the HOMA index. Conclusions: The UGT2B15 D(85)Y and the UGT2B17 deletion polymorphisms are both predictors of the glucuronidation pattern of androgens/androgen metabolites. Our findings indicate that UGT2B17 is involved in 17 glucuronidation of mainly T but also of DHT and androstanediol and that UGT2B15 is involved in the 17 glucuronidation of androstanediol. Furthermore, these two polymorphisms are predictors of fat mass in men.
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