scholarly journals Association of CYP3A7*1C and Serum Dehydroepiandrosterone Sulfate Levels in Women with Polycystic Ovary Syndrome

2008 ◽  
Vol 93 (7) ◽  
pp. 2909-2912 ◽  
Author(s):  
Mark O. Goodarzi ◽  
Ning Xu ◽  
Ricardo Azziz
Keyword(s):  
Los Angeles ◽  
Polycystic Ovary Syndrome ◽  
White Women ◽  
Polycystic Ovary ◽  
Medical Center ◽  
Free Testosterone ◽  
Total Testosterone ◽  
Adrenal Androgen ◽  
Androgen Excess ◽  
Ovary Syndrome

Abstract Context: Adrenal androgen excess is common in polycystic ovary syndrome (PCOS) and appears to be heritable. CYP3A7 metabolizes dehydroepiandrosterone and its sulfate (DHEAS). A promoter variant, CYP3A7*1C, which results in persistent expression in adults, was associated with reduced DHEAS levels in a previous study, which led us to consider CYP3A7*1C as a modulator of adrenal androgen excess in patients with PCOS. Objective: The objective was to replicate the association between CYP3A7*1C and reduced DHEAS levels in PCOS patients and assess its possible role in modulating testosterone levels. Design: Women with and without PCOS were genotyped for CYP3A7*1C, and this variant was tested for association with DHEAS and total and free testosterone. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center (Los Angeles, CA). Participants: A total of 287 white women with PCOS and 187 controls were studied. Main Measurements: CYP3A7*1C genotype, PCOS risk, and androgen levels were measured. Results: PCOS subjects who carried the CYP3A7*1C variant had lower levels of serum DHEAS and total testosterone (P = 0.0006 and 0.046, respectively). The variant was not associated with PCOS risk. Conclusion: This study replicated prior work of the association of CYP3A7*1C and decreased DHEAS in a different population of young PCOS women, providing further genetic evidence that CYP3A7 plays a potential role in modulation of DHEAS levels. Adult expression of CYP3A7 may modify the PCOS phenotype by ameliorating adrenal androgen excess.

scholarly journals Genes for Enzymes Regulating Dehydroepiandrosterone Sulfonation Are Associated with Levels of Dehydroepiandrosterone Sulfate in Polycystic Ovary Syndrome

2007 ◽  
Vol 92 (7) ◽  
pp. 2659-2664 ◽  
Author(s):  
Mark O. Goodarzi ◽  
Heath J. Antoine ◽  
Ricardo Azziz
Keyword(s):  
Los Angeles ◽  
Polycystic Ovary Syndrome ◽  
White Women ◽  
Polycystic Ovary ◽  
Medical Center ◽  
Dehydroepiandrosterone Sulfate ◽  
Nucleotide Polymorphisms ◽  
Adrenal Androgen ◽  
Ovary Syndrome ◽  
Dheas Level

Abstract Context: The adrenal androgen (AA) metabolite dehydroepiandrosterone sulfate (DHEAS) is often elevated in women with polycystic ovary syndrome (PCOS); AA excess in PCOS appears to be, in part, a heritable trait. Dehydroepiandrosterone (DHEA) sulfonation is controlled by the enzymes DHEA sulfotransferase (SULT2A1) and steroid sulfatase (STS). Polymorphisms in these genes have not been evaluated as modulators of DHEAS level in PCOS. Objective: The aim was to test the hypothesis that variants in the SULT2A1 and STS genes are associated with DHEAS levels in women with PCOS. Design: Women with and without PCOS were genotyped for seven single nucleotide polymorphisms (SNPs) in SULT2A1 and seven SNPs in STS. SNPs and haplotypes were determined and tested for association with DHEAS. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. Participants: A total of 287 white women with PCOS and 187 controls participated in the study. Main Measurements: SULT2A1 and STS genotype and DHEAS levels were measured. Results: In women with PCOS, SNP rs182420 in SULT2A1 was associated with DHEAS (P = 0.0035). Two haplotypes carrying the minor allele of rs182420 were also associated with DHEAS (P = 0.04 each). Variants within STS were not associated with DHEAS level. No associations were observed in control women. Conclusion: This study presents genetic evidence suggesting a potential role of SULT2A1, but not STS, in the inherited AA excess of PCOS.

scholarly journals Association of oral contraceptive and metformin did not improve insulin resistance in women with polycystic ovary syndrome

2015 ◽  
Vol 61 (3) ◽  
pp. 215-219 ◽  
Author(s):  
Margareth Chiharu Iwata ◽  
Livia Porquere ◽  
Isabel C. Espósito Sorpreso ◽  
Edmund C. Baracat ◽  
José Maria Soares Júnior
Keyword(s):  
Insulin Resistance ◽  
Oral Contraceptive ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Total Testosterone ◽  
Model Assessment ◽  
Cycle Index ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Improve Insulin Resistance

Summary Objective: Objective: to compare clinical and laboratory parameters in women with polycystic ovary syndrome (PCOS) using metformin or combined oral contraceptive (COC) after 6 months. Methods: retrospective study analyzing records of patients with PCOS using the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society criteria. The groups were: I-COC (21 tablets, pause of 7 days; n=16); II-metformin (850mg 12/12h, n=16); III-COC plus metformin (n=9). Body mass index (BMI), acne (% of improvement), modified Ferriman-Gallway index and menstrual cycle index (MCI), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), androstenedione (A) and homeostasis model assessment: insulin resistance (HOMA-IR) index were assessed Results: isolated use of COC compared to metformin was better regarding to acne, Ferriman index, MCI, LH, TT and A levels. On the other hand, metformin was better in the HOMA-IR index (4.44 and 1.67 respectively, p=0.0007). The association COC plus metformin, compared to metformin alone shows the maintenance of improvement of acne, Ferriman index, MCI, and testosterone levels. The HOMA-IR index remained lower in the metformin alone group (4.19 and 1.67, respectively; p=0,046). The comparison between COC plus metformin and COC alone, in turn, shows no difference in the improvement of acne, Ferriman index, MCI, LH, TT and A levels, indicating that the inclusion of metformin did not lead to additional benefits in these parameters. Still, the HOMA-IR index was similar in both groups (4.19 and 4.44 respectively; p=0.75), showing that the use of metformin associated with COC may not improve insulin resistance as much as it does if used alone. Conclusion: our data suggest that the combination of metformin and contraceptive does not improve insulin resistance as observed with metformin alone.

scholarly journals Variants in the 5α-Reductase Type 1 and Type 2 Genes Are Associated with Polycystic Ovary Syndrome and the Severity of Hirsutism in Affected Women

2006 ◽  
Vol 91 (10) ◽  
pp. 4085-4091 ◽  
Author(s):  
Mark O. Goodarzi ◽  
Nissar A. Shah ◽  
Heath J. Antoine ◽  
Marita Pall ◽  
Xiuqing Guo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Los Angeles ◽  
Single Nucleotide Polymorphisms ◽  
Polycystic Ovary Syndrome ◽  
White Women ◽  
Polycystic Ovary ◽  
Nucleotide Polymorphisms ◽  
Ovary Syndrome ◽  
Single Nucleotide ◽  
Control Subjects

Abstract Context: Despite the importance of dihydrotestosterone in androgen action, polymorphisms in the genes for the two isoforms of 5α-reductase (SRD5A1 and SRD5A2) have not been evaluated as risk factors for polycystic ovary syndrome (PCOS). Objective: The objective of the study was to test the hypothesis that haplotypes in the SRD5A1 and SRD5A2 genes are risk factors for PCOS and the severity of hirsutism in affected women. Design: PCOS and control subjects were genotyped for seven single-nucleotide polymorphisms in SRD5A1 and eight single-nucleotide polymorphisms in SRD5A2. Haplotypes were determined and tested for association with PCOS diagnosis and component phenotypes. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; control subjects were recruited from the general surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. Participants: A total of 287 White women with PCOS and 187 controls participated. Main Measurements: SRD5A1 and SRD5A2 genotype, quantitative hirsutism score, and hormonal and metabolic phenotypes were assessed. Results: Haplotypes within both genes were associated with PCOS risk. The Leu allele of the Val89Leu variant in SRD5A2 was associated with protection against PCOS; this allele is known to modestly reduce 5α-reductase activity. Haplotypes in SRD5A1 but not SRD5A2 were also associated with the degree of hirsutism in affected women. Conclusions: This study presents genetic evidence suggesting an important role of both isoforms of 5α-reductase in the pathogenesis of PCOS. That only SRD5A1 haplotypes were associated with hirsutism suggests that only this isoform is important in the hair follicle.

Adrenal androgen excess and body mass index in polycystic ovary syndrome

2015 ◽  
pp. jc.0000-9999 ◽  
Author(s):  
Carlos Moran ◽  
Monica Arriaga ◽  
Fabian Arechavaleta-Velasco ◽  
Segundo Moran
Keyword(s):  
Body Mass Index ◽  
Polycystic Ovary Syndrome ◽  
Body Mass ◽  
Polycystic Ovary ◽  
Adrenal Androgen ◽  
Androgen Excess ◽  
Ovary Syndrome

scholarly journals Testosterone or Dehydroepiandrosterone Sulfate as a Biomarker for Hirsutism in Women with Polycystic Ovary Syndrome

2020 ◽  
Vol 13 (4) ◽  
pp. 1815-1823
Author(s):  
Husam Jihad Imran ◽  
Samer Abdulameer Dhaher ◽  
Abbas Ali Mansour
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Free Testosterone ◽  
Dehydroepiandrosterone Sulfate ◽  
Medical Problem ◽  
Total Testosterone ◽  
Ovary Syndrome ◽  
Healthy Control ◽  
Control Study ◽  
Rotterdam Criteria

Background:Hirsutism is a distressing medical problem for women. Most of hirsutism in women is associated with excess androgen, and most cases have PCOS as an underlying cause.Which androgen to be used to evaluate clinical or biochemical hyperandrogenism in women with PCOS is still debated.There are a small number of studies that evaluated androgens in women with PCOS having hirsutism with conflicting results. The Objective of this study was to determine which androgen predict hirsutism in women with polycystic ovary syndrome (PCOS). Patients and Methods:A case-control study was done in Faiha Specialized Diabetes, Endocrine, and Metabolism Center (FDEMC), Basrah, Iraq. A total of 130 women with PCOS (based on Rotterdam criteria) and 70 healthy controls of comparable age (16-40 years) were investigated for androgens (total testosterone, free testosterone, DHEA-S) using Electrochemiluminescence technology assay; excess hair was examined according to the modified Ferriman-Gallwey (mFG) score and a cut-off value of 8 defined hirsutism. Results: In the three groups of women, the first (n=100) included PCOS with hirsutism, the second (n=30) PCOS without hirsutism, and the third (n=70) women without PCOS or hirsutism as healthy control, hirsutism was seen in about 77 % of PCOS women mostly of moderate severity; High TT, FT, DHEA-S, and overall androgens were seen in 69%, 76%, 37%, and 99% respectively of our PCOS women with hirsutism. No correlation was found between TT, FT, and DHEA-S and the mFG score. Conclusions: This study provides evidence that presence of hirsutism in women with PCOS was associated with a higher level of biochemical hyperandrogenism than seen in PCOS without hirsutism; however, there was no correlation between the studied androgens and mFG score.

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