Pharmacological Differences between Men and Women

Chen, Maylee; Bertino, Joseph S.; Berg, Mary; Nafziger, Anne N.

doi:10.1016/b978-012369417-1/50061-4

Cited by 3 publications

(6 citation statements)

References 107 publications

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“…The difference between males and females in both cholesterol control whilst on simvastatin or atorvastatin treatment, and in likelihood of discontinuing treatment, may have implications for interventions (specific statin prescribed and dose) and subsequent cardiovascular outcomes. This significant interaction between SLCO1B1*5 genotype and sex could be due to females having lower mean muscle mass and body weight, and higher percentage of body fat compared to males, leading to higher concentrations of simvastatin and atorvastatin, 25 with SLCO1B1*5 therefore causing increased discontinuation of treatment due to side effects. 12 Although we observe raised cholesterol levels in SLCO1B1*5…”

Section: Discussionmentioning

confidence: 99%

“… 23 Current UK clinical recommendations are to begin atorvastatin treatment when 10‐year CVD risk is >10% and to assess statin effectiveness if 40% reduction in non‐HDL cholesterol is achieved 3 months after treatment initiation. 24 Women have lower body weight and a higher percentage of body fat compared to men, which might lead to higher concentrations of lipophilic drugs such as simvastatin and atorvastatin, 25 and increased risk of adverse events, which may be exacerbated by the SLCO1B1 *5 decreased function genotype, which increases concentrations of drugs due to less uptake of the drug. 12 …”

Section: Introductionmentioning

confidence: 99%

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Statin treatment effectiveness and the *SLCO1B1**5 reduced function genotype: Long‐term outcomes in women and men

Türkmen

Masoli

Kuo

et al. 2022

Brit J Clinical Pharma

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Objective To estimate the effect of rs4149056 (SLCO1B1*5) genotype (decreases statin transport) on cholesterol control and treatment duration in male and female primary care patients prescribed common statin medications. Methods and Analysis This study comprised 69 185 European‐ancestry UK Biobank cohort participants prescribed simvastatin or atorvastatin (aged 40‐79 years at first prescription, treatment duration 1 month to 29 years, mean 5.7 years). Principal outcomes were clinically high total cholesterol (>5 mmol/L) at baseline, plus treatment discontinuation. Results A total of 48.4% of 591 females homozygous for SLCO1B1*5 decreased function genotype had raised cholesterol vs 41.7% of those with functioning SLCO1B1 (odds ratio 1.31, 95% confidence interval [CI] 1.1‐1.55, P = .001). Fewer males had high cholesterol and the genotype effect was attenuated. In primary care prescribing, females homozygous for SLCO1B1*5 were more likely to stop receiving these statins (29.5%) than women with normal SLCO1B1 (25.7%) (hazard ratio [HR] 1.19, 95% CI 1.03‐1.37, P = .01), amounting to five discontinuations per 100 statin‐years in the SLCO1B1*5 group vs four in the normal SLCO1B1 function group. This remained significant after the first year of treatment (HR for discontinuing >1 year after first prescription 1.3, 95% CI 1.08‐1.56, P = .006). In men SLCO1B1*5 was only associated with treatment discontinuation in the first year. Conclusions In this large community sample of patients on commonly prescribed statins, the SLCO1B1*5 decreased function variant had much larger effects on cholesterol control and treatment duration in women than in men. Efforts to improve the effectiveness of statin therapy in women may need to include SLCO1B1*5 genotype‐guided statin selection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Statin treatment effectiveness and the *SLCO1B1**5 reduced function genotype: Long‐term outcomes in women and men

Türkmen

Masoli

Kuo

et al. 2022

Brit J Clinical Pharma

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“…Studies from other systems reveal important findings in this regard. Sex differences in response to therapeutic agents based on both pharmacokinetic and pharmacodynamic factors are being increasingly recognized [Chen et al, 2007;Franconi et al, 2007]. There are sexually dimorphic effects of glucocorticoids on gene expression in rat liver, effects potentially relevant to sex differences in susceptibility to inflammatory disease [Duma et al, 2010].…”

Section: Discussionmentioning

confidence: 99%

Sex-specific effects of estrogen and androgen on gene expression in human monocyte-derived osteoclasts

Wang

Stern

2011

J. Cell. Biochem.

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Estrogen and androgen are both critical for the maintenance of bone, but the target cells, mechanisms, and responses could be sex-specific. To compare sex-specific actions of estrogen and androgen on osteoclasts, human peripheral blood mononuclear precursor cells from adult Caucasian males (n = 3) and females (n = 3) were differentiated into osteoclasts and then treated for 24 h with 17β-estradiol (10 nM) or testosterone (10 nM). Gene expression was studied with a custom designed qPCR-based array containing 94 target genes related to bone and hormone action. In untreated osteoclasts, 4 genes showed significant gender differences. 17β-estradiol significantly affected 12 genes in osteoclasts from females and 6 genes in osteoclasts from males. Fifteen of the 18 17β-estradiol-responsive genes were different in the cells from the two sexes; 2 genes affected by 17β-estradiol in both sexes were regulated oppositely in the two sexes. Testosterone significantly affected 6 genes in osteoclasts from females and 2 genes in osteoclasts from males; all except one were different in the two sexes. 17β-estradiol and testosterone largely affected different genes, suggesting that conversion of testosterone to 17β-estradiol had a limited role in the responses. The findings indicate that although osteoclasts from both sexes respond to 17β-estradiol and testosterone, the effects of both 17β-estradiol and testosterone differ in the two sexes, highlighting the importance of considering gender in the design of therapy.

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“…The difference between males and females in both cholesterol control whilst on simvastatin or atorvastatin treatment, and in likelihood of discontinuing treatment, may have implications for interventions (specific statin prescribed, and dose) and subsequent cardiovascular outcomes. This significant interaction between SLCO1B1 *5 genotype and sex could be due to females having lower mean muscle mass and body weight, and higher percentage of body fat compared to males, leading to higher concentrations of unmetabolized simvastatin and atorvastatin (24), with SLCO1B1 *5 therefore causing increased discontinuation of treatment due to side effects (12).…”

Section: Discussionmentioning

confidence: 99%

“…Current UK clinical recommendations are to begin atorvastatin treatment when 10-year CVD risk is >10% and to assess statin effectiveness if 40% reduction in non-HDL cholesterol is achieved 3 months after treatment initiation (23). Women have lower body weight and a higher percentage of body fat compared to men, which might lead to higher concentrations of lipophilic drugs such as simvastatin and atorvastatin (24) and increased risk of adverse events, which may be exacerbated by the SLCO1B1 *5 decreased function genotype which increases concentrations of unmetabolized drugs (12).…”

Section: Introductionmentioning

confidence: 99%

Statin treatment effectiveness and the *SLCO1B1**5 reduced function genotype: long-term outcomes in women and men

Türkmen

Masoli

Kuo

et al. 2021

Preprint

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Objective: To estimate the effect of the SLCO1B1*5 genotype (decreases statin transport) on cholesterol control and treatment duration in male and female primary care patients prescribed common statin medications. Methods and Analysis: 69,185 European-ancestry UK Biobank cohort participants prescribed simvastatin or atorvastatin (aged 40 to 79 years at first prescription; treatment duration 1 month to 29 years, mean 5.7 years). Principal outcomes were clinically high total cholesterol (>5mmol/L) at baseline, plus treatment discontinuation. Results: 48.4% of 591 females homozygous for SLCO1B1*5 decreased function genotype had raised cholesterol, vs. 41.7% of those with functioning SLCO1B1 (Odds Ratio 1.31: 95% Confidence Intervals 1.1 to 1.55, p=0.001). Fewer males had high cholesterol, and the genotype effect was attenuated. In primary care prescribing, females homozygous for SLCO1B1*5 were more likely to stop receiving these statins (29.5%) than women with normal SLCO1B1 (25.7%) (Hazard Ratio 1.19: 95%CI 1.03 to 1.37, p=0.01), amounting to five discontinuations per 100 statin-years in the SLCO1B1*5 group vs four in the normal SLCO1B1 function group. This remained significant after the first year of treatment (HR for discontinuing >1 year after first prescription 1.3: 95%CI 1.08 to 1.56; p=0.006). In men SLCO1B1*5 was only associated with treatment discontinuation in the first year. Conclusions: In this large community sample of patients on commonly prescribed statins, the SLCO1B1*5 decreased function variant had much larger effects on cholesterol control and treatment duration in women than in men. Efforts to improve effectiveness of statin therapy in women may need to include SLCO1B1*5 genotype-guided statin selection.

show abstract

Pharmacological Differences between Men and Women

Cited by 3 publications

References 107 publications

Statin treatment effectiveness and the *SLCO1B1**5 reduced function genotype: Long‐term outcomes in women and men

Statin treatment effectiveness and the *SLCO1B1**5 reduced function genotype: Long‐term outcomes in women and men

Sex-specific effects of estrogen and androgen on gene expression in human monocyte-derived osteoclasts

Statin treatment effectiveness and the *SLCO1B1**5 reduced function genotype: long-term outcomes in women and men

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Pharmacological Differences between Men and Women

Cited by 3 publications

References 107 publications

Statin treatment effectiveness and the SLCO1B1*5 reduced function genotype: Long‐term outcomes in women and men

Statin treatment effectiveness and the SLCO1B1*5 reduced function genotype: Long‐term outcomes in women and men

Sex-specific effects of estrogen and androgen on gene expression in human monocyte-derived osteoclasts

Statin treatment effectiveness and the SLCO1B1*5 reduced function genotype: long-term outcomes in women and men

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Statin treatment effectiveness and the *SLCO1B1**5 reduced function genotype: Long‐term outcomes in women and men

Statin treatment effectiveness and the *SLCO1B1**5 reduced function genotype: Long‐term outcomes in women and men

Statin treatment effectiveness and the *SLCO1B1**5 reduced function genotype: long-term outcomes in women and men