Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome.
CONTEXT: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, and susceptibility to the metabolic syndrome. Altered peripheral cortisol metabolism has been reported in PCOS, but also in simple obesity. OBJECTIVE: The aim of the study was to describe cortisol metabolis...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2009
|
| _version_ | 1826291548811165696 |
|---|---|
| author | Vassiliadi, D Barber, T Hughes, B McCarthy, M Wass, J Franks, S Nightingale, P Tomlinson, J Arlt, W Stewart, P |
| author_facet | Vassiliadi, D Barber, T Hughes, B McCarthy, M Wass, J Franks, S Nightingale, P Tomlinson, J Arlt, W Stewart, P |
| author_sort | Vassiliadi, D |
| collection | OXFORD |
| description | CONTEXT: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, and susceptibility to the metabolic syndrome. Altered peripheral cortisol metabolism has been reported in PCOS, but also in simple obesity. OBJECTIVE: The aim of the study was to describe cortisol metabolism and metabolic characteristics of a large PCOS cohort and to delineate the effect of obesity by comparison to body mass index (BMI)-matched controls. DESIGN AND SETTING: We conducted an observational, cross-sectional study at outpatient clinics of two secondary/tertiary care centers. PATIENTS OR OTHER PARTICIPANTS: A total of 178 PCOS patients fulfilling Rotterdam criteria and 100 BMI-matched controls participated in the study. INTERVENTION: The study included 24-h urine collection for steroid metabolite excretion and fasting blood samples, followed by an oral glucose tolerance test. MAIN OUTCOME MEASURES: We measured urinary steroid metabolites including glucocorticoids and androgens and the ratios reflecting enzymatic activities involved in peripheral cortisol and androgen metabolism, 5 alpha-reductase, and 11 beta-hydroxysteroid dehydrogenase types 1 and 2. We also measured circulating levels of glucose, insulin, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone and calculated homeostasis model assessment. RESULTS: Total androgen metabolites were higher in PCOS patients compared to BMI-matched controls (4,105 +/- 2,047 vs. 2,532 +/- 1,610 microg/24 h for the nonobese; 5,547 +/- 2,911 vs. 2,468 +/- 1,794 microg/24 h for the obese; both P < 0.001). Total glucocorticoid metabolites were higher in obese PCOS vs. controls (10,786 +/- 3,852 vs. 8,834 +/- 4,487 microg/24 h; P = 0.001). 5 alpha-Reductase activity correlated with BMI, insulin levels, and homeostasis model assessment. Both obese and nonobese PCOS patients had higher 5 alpha-reductase activity than controls (all P < 0.05). 11 beta-Hydroxysteroid dehydrogenase activities did not differ between PCOS and controls. CONCLUSIONS: PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5 alpha-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS. |
| first_indexed | 2024-03-07T03:01:03Z |
| format | Journal article |
| id | oxford-uuid:b0f8eac1-636d-4e41-89c2-007be4464455 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:01:03Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:b0f8eac1-636d-4e41-89c2-007be44644552022-03-27T04:00:27ZIncreased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b0f8eac1-636d-4e41-89c2-007be4464455EnglishSymplectic Elements at Oxford2009Vassiliadi, DBarber, THughes, BMcCarthy, MWass, JFranks, SNightingale, PTomlinson, JArlt, WStewart, P CONTEXT: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, and susceptibility to the metabolic syndrome. Altered peripheral cortisol metabolism has been reported in PCOS, but also in simple obesity. OBJECTIVE: The aim of the study was to describe cortisol metabolism and metabolic characteristics of a large PCOS cohort and to delineate the effect of obesity by comparison to body mass index (BMI)-matched controls. DESIGN AND SETTING: We conducted an observational, cross-sectional study at outpatient clinics of two secondary/tertiary care centers. PATIENTS OR OTHER PARTICIPANTS: A total of 178 PCOS patients fulfilling Rotterdam criteria and 100 BMI-matched controls participated in the study. INTERVENTION: The study included 24-h urine collection for steroid metabolite excretion and fasting blood samples, followed by an oral glucose tolerance test. MAIN OUTCOME MEASURES: We measured urinary steroid metabolites including glucocorticoids and androgens and the ratios reflecting enzymatic activities involved in peripheral cortisol and androgen metabolism, 5 alpha-reductase, and 11 beta-hydroxysteroid dehydrogenase types 1 and 2. We also measured circulating levels of glucose, insulin, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone and calculated homeostasis model assessment. RESULTS: Total androgen metabolites were higher in PCOS patients compared to BMI-matched controls (4,105 +/- 2,047 vs. 2,532 +/- 1,610 microg/24 h for the nonobese; 5,547 +/- 2,911 vs. 2,468 +/- 1,794 microg/24 h for the obese; both P < 0.001). Total glucocorticoid metabolites were higher in obese PCOS vs. controls (10,786 +/- 3,852 vs. 8,834 +/- 4,487 microg/24 h; P = 0.001). 5 alpha-Reductase activity correlated with BMI, insulin levels, and homeostasis model assessment. Both obese and nonobese PCOS patients had higher 5 alpha-reductase activity than controls (all P < 0.05). 11 beta-Hydroxysteroid dehydrogenase activities did not differ between PCOS and controls. CONCLUSIONS: PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5 alpha-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS. |
| spellingShingle | Vassiliadi, D Barber, T Hughes, B McCarthy, M Wass, J Franks, S Nightingale, P Tomlinson, J Arlt, W Stewart, P Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome. |
| title | Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome. |
| title_full | Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome. |
| title_fullStr | Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome. |
| title_full_unstemmed | Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome. |
| title_short | Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome. |
| title_sort | increased 5 alpha reductase activity and adrenocortical drive in women with polycystic ovary syndrome |
| work_keys_str_mv | AT vassiliadid increased5alphareductaseactivityandadrenocorticaldriveinwomenwithpolycysticovarysyndrome AT barbert increased5alphareductaseactivityandadrenocorticaldriveinwomenwithpolycysticovarysyndrome AT hughesb increased5alphareductaseactivityandadrenocorticaldriveinwomenwithpolycysticovarysyndrome AT mccarthym increased5alphareductaseactivityandadrenocorticaldriveinwomenwithpolycysticovarysyndrome AT wassj increased5alphareductaseactivityandadrenocorticaldriveinwomenwithpolycysticovarysyndrome AT frankss increased5alphareductaseactivityandadrenocorticaldriveinwomenwithpolycysticovarysyndrome AT nightingalep increased5alphareductaseactivityandadrenocorticaldriveinwomenwithpolycysticovarysyndrome AT tomlinsonj increased5alphareductaseactivityandadrenocorticaldriveinwomenwithpolycysticovarysyndrome AT arltw increased5alphareductaseactivityandadrenocorticaldriveinwomenwithpolycysticovarysyndrome AT stewartp increased5alphareductaseactivityandadrenocorticaldriveinwomenwithpolycysticovarysyndrome |