Health differences in Women and Men

Reference: Clinical Chemistry and Laboratory Medicine. Volume 51, Issue 4, Pages 713–727, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/cclm-2012-0849, March 2013

• Men: Increased rate of liver fibrosis progression: age at infection older than 40 years, daily alcohol consumption of 50 g or more and male sex. Liver in 25.8% of men and in 20.3% in females ; the mean age of males with fatty liver was 43.3±1.2 years versus 56.5±1.1 in women
• Men: Genetic hemochromatosis/Iron Overload , prevalence is higher in males than in females

• Women: Menstruation can play an important role in reducing the toxic effect of iron accumulation.
• Women are more prone to the development of side effects and different pharmacological response to drug treatment.

Women: Systemic Lupus Erythematosus. SLE is an autoimmune disorder characterized by the production of pathogenic autoantibodies, primarily to nuclear antigens, as well as dysregulation of both T and B cells. B cells display accelerated maturity. SLE patients exhibit monocyte-derived DCs, which display an activated, proinflammatory phenotype. SLE has a female preponderance of 9:1. Although there are X-chromosome abnormalities associated with SLE, estrogen itself is strongly implicated in SLE autoimmunity. SLE is associated with a disrupted sex hormone balance characterized by lower amounts of androgens and dramatically higher levels of the estrogen metabolite.

Women are more prone to drug side-effects: CYP3A4 ligands, enzymes involved in the metabolism of xenobiotics in the human body. Xenobiotics are potentially harm-ful, lipid-soluble chemicals that are foreign to the human body.
Following is a table of selected substrates/participants, inducers/increase and inhibitors/decrease of CYP3A4. Where classes of agents are listed, there may be exceptions within the class.
Inhibitors of CYP3A4 can be classified by their potency, such as:
• Strong inhibitor being one that causes at least a 5-fold increase in the plasma AUC values, or more than 80% decrease in clearance.
• Moderate inhibitor being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance.
• Weak inhibitor being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20-50% decrease in clearance.

Selected inducers, inhibitors and substrates of CYP3A4

Substrates/Participants Inhibitors/Decrease Inducers/Increase
• some immunosuppressants
o ciclosporin (cyclosporin) [27][29]
o tacrolimus[27][29]
o sirolimus[27][29]
• many chemotherapeutic
o docetaxel[27][29]
o tamoxifen[27][29]
o paclitaxel[27][29]
o cyclophosphamide[29]
o doxorubicin[29]
o erlotinib[30]
o etoposide[29]
o ifosfamide[29]
o teniposide[29]
o vinblastine[29]
o vincristine[27]
o vindesine[29]
o imatinib[27]
o irinotecan[27]
o sorafenib[27]
o sunitinib[27]
o temsirolimus[27]
o anastrazole
o gefitinib
• azole antifungals
o ketoconazole[29]
o itraconazole[29]
• macrolides
o clarithromycin[27][29]
o erythromycin[27]
o telithromycin[27]
(not azithromycin)[27]
• dapsone[27] (in leprosy)
• tricyclic antidepressants
o amitriptyline[29]
o clomipramine[29]
o imipramine[29]
o citalopram[29]
o norfluoxetine[29]
o sertraline[29]
• some other antidepressants
o mirtazapine[29] (NaSSA)
o nefazodone[29]
o reboxetine[29]
o venlafaxine[29] (SNRI)
o trazodone[27] (SARI
• buspirone[27][29] (anxiolytic)
• antipsychotics
o haloperidol[27][29]
o aripiprazole[27]
o risperidone[27]
o ziprasidone[27]
o pimozide[29]
o quetiapine[27]
• opioids (mainly analgesics)
o alfentanil[27][29]
o buprenorphine[31]
o codeine[27] (analgesic, antitussive, antidiarrheal)
o fentanyl[27]
o methadone[27] (analgesic, anti-addictive)
o levacetylmethadol[27]
• benzodiazepines
o alprazolam[27][29]
o midazolam[27][29]
o triazolam[27][29]
o diazepam[27]
• some hypnotics
o zopiclone[29]
o zaleplon[27]
o zolpidem[27]
• donepezil[29] (acetylcholinesterase inhibitor)
• statins
o atorvastatin[27][29]
o lovastatin[27][29]
o simvastatin[29]
o cerivastatin[27]
(not pravastatin)[27]
(not rosuvastatin)[27]
• calcium channel blockers
o diltiazem[27][29]
o felodipine[27][29]
o nifedipine[27][29]
o verapamil[27][29]
o amlodipine[27]
o lercanidipine[27]
o nitrendipine[27]
o nisoldipine[27]
• amiodarone[29] (class III antiarrhythmic)
• dronedarone[29] (class III antiarrhythmic)
• quinidine[27] (class I antiarrhythmic)
• PDE5 inhibitors
o sildenafil[27][29]
o tadalafil[32]
• kinins[29] (vasodilators, smooth muscle contractors)
• sex hormones agonists and antagonists
o finasteride[27][29] (antiandrogen)
o estradiol[27] (estrogen)
o progesterone[27]
o ethinylestradiol[29] (hormonal contraceptive)
o testosterone[27] (androgen)
o toremifene[29] (SERM)
o bicalutamide [33]
• H1-receptor antagonists
o terfenadine[27][29]
o astemizole[27][34]
o chlorphenamine[27]
• Protease inhibitors
o indinavir[27][29]
o ritonavir[27][29]
o saquinavir[27][29]
o nelfinavir[27][29]
• non-nucleoside reverse transcriptase inhibitors
o nevirapine[29]
• some glucocorticoids
o budesonide[29]
o hydrocortisone[27]
o dexamethasone[27]
• cisapride[27][29] (5-HT4 receptor agonist)
• aprepitant[27] (antiemetic)
• caffeine[27] (stimulant)
• cocaine[27] (stimulant)
• cilostazol[27] (phosphodiesterase inhibitor)
• dextromethorphan[27] (antitussive)
• domperidone[27] (antidopaminergic)
• eplerenone[27] (aldosterone antagonist)
• lidocaine[27] (local anesthetic, antiarrhythmic)
• ondansetron[27] (5-HT3 antagonist)
• propranolol[27] (beta blocker)
• salmeterol[27] (beta agonist)
• warfarin[35] (anticoagulant)
• clopidogrel, becoming bioactivated[36] (antiplatelet)
• esomeprazole[29] (proton pump inhibitor)
• nateglinide[27] (antidiabetic)
• protease inhibitors
o ritonavir[27][29][37]
o indinavir[27]
o nelfinavir[27]
o saquinavir[27]
• some macrolide antibiotics[37]
o clarithromycin[27][29]
o telithromycin[27]
• chloramphenicol (antibiotic)[38]
• some azole antifungals
o ketoconazole[27][29]
o itraconazole[27][29]
• nefazodone[27][29] (antidepressant)
• aprepitant[27] (antiemetic)
• some calcium channel blockers
o verapamil[27]
o diltiazem[27]
• some macrolide antibiotics
o erythromycin[27]
• some azole antifungals[37]
o fluconazole[27]
• bergamottin (constituent of grapefruit juice)[27]
• Valerian [39]
• cimetidine[27] (H2-receptor antagonist)
• buprenorphine (analgesic)[40]
• cafestol (in unfiltered coffee)[41]
unspecified potency:
• amiodarone[27] (antiarrhythmic)
• bicalutamide[33]
• ciprofloxacin[27] (antibiotic)
• dithiocarbamate[27] (functional group)
• voriconazole[27] (antifungal)
• imatinib[27] (anticancer)
• mifepristone[27] (abortifacient)
• norfloxacin[27] (antibiotic)
• some non-nucleoside reverse transcriptase inhibitors[42]
o delavirdine[27]
• gestodene[27] (hormonal contraceptive)
• mibefradil[27] (in angina pectoris)
o fluoxetine/norfluoxetine[27]
o fluvoxamine[27]
• star fruit[27][43]
• milk thistle[44]
• ginko biloba[45]
• quercetin – Quercetin has been shown to act as an initial inhibitor and subsequent inducer.[46]
• piperine[47]
• anticonvulsants, mood stabilizers
o carbamazepine[27][29][37]
o phenytoin[27][29] (anticonvulsant)
o oxcarbazepine[27]
• barbiturates[37]
o phenobarbital[27][29]
• St. John’s wort[27][29]
• some bactericidals
o rifampicin[27][37]
o rifabutin[27][29]
• some non-nucleoside reverse transcriptase inhibitors [42]
o efavirenz[27]
o nevirapine[27]
• some hypoglycemics
o pioglitazone[27]
o troglitazone[27]
• glucocorticoids[27] (blood glucose increase, immunosuppressive)

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