Clinical Pharmacokinetics

, Volume 34, Issue 3, pp 203–218 | Cite as

Physiological Changes During the Menstrual Cycle and Their Effects on the Pharmacokinetics and Pharmacodynamics of Drugs

Review Articles Special Populations


There is an increasing awareness that the exclusion of women from clinical trials may lead to inaccurate application of drug therapy in women. Gender and estrus cycle differences in the pharmacokinetics and pharmacodynamics of drugs in animals have been appreciated for over 60 years, but investigation into these differences in humans has only recently occurred.

It is postulated that hormonal fluctuations within the menstrual cycle phase may be a primary cause of documented gender differences in the pharmacokinetics and pharmacodynamics of drugs. Existing data suggest that menstrual cycle variations do occur in renal, cardiovascular, haematological and immune systems. These physiological changes could potentially impact on the pharmacokinetics or pharmacodynamics of drugs by altering properties, such as protein binding or the volume of distribution, and thereby causing significant effects at various times during the menstrual cycle. However, systematic investigations of physiological variability throughout the menstrual cycle are limited.

Fluctuations in symptom severity and clinical course coinciding with the menstrual cycle phase have been seen in some diseases. Hormonal fluctuations within the menstrual cycle have been postulated to cause disease exacerbation. They may also worsen disease severity by impacting on the pharmacokinetics or pharmacodynamics of the medication.

Menstrual cycle hormonal changes may influence drug absorption, distribution, metabolism or excretion. In vivo data to demonstrate an effect of endogenous estrogen or progesterone on pharmacokinetics are limited and contradictory.

Systematic investigations of specific pharmacokinetic and pharmacodynamic changes within the menstrual cycle are lacking. Most published studies have been conducted with small numbers of women and a limited numbers of menstrual cycle phases within 1 menstrual cycle. These design problems have resulted in incomplete data for assessing the effects of the menstrual cycle. To date, there are no demonstrated clinically significant changes that occur in the absorption, distribution or elimination of drugs. With respect to drug metabolism, data are exceedingly sparse and have been collected in a suboptimal fashion. Standardisation of study design and analyses in systematic investigations of the influence of the menstrual cycle on drug pharmacokinetics and pharmacodynamics are needed.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Nicholas GS, Barron DH. The use of sodium amytal in the production of anesthesia in the rat. J Pharmacol Exp Ther. 1932; 46: 125–9.Google Scholar
  2. 2.
    Brandstetter Y, Kaplanski J, Leibson V, et al. The effects of estrus cycle on drug metabolism in the rat. Eur J Drug Metab Pharmacokinet. 1986; 11(4): 251–4.PubMedCrossRefGoogle Scholar
  3. 3.
    Kato R. Sex-related differences in drug metabolism. Drug Metab Rev. 1974; 3: 1–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Skett P. Biochemical basis of sex differences in drug metabolism. Pharmacol Ther. 1988; 38: 269–304.PubMedCrossRefGoogle Scholar
  5. 5.
    Gleiter CH, Gundert-Remy U. Gender differences in pharmacokinetics. Eur J Drug Metab Pharmacokinet. 1996; 21: 123–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Fletcher CV, Acosta EP, Strykowski JM. Gender differences in human pharmacokinetics and pharmacodynamics. J Adolesc Health. 1994; 15: 619–29.PubMedCrossRefGoogle Scholar
  7. 7.
    Harris RZ, Benet LZ, Schwartz JB. Gender effects in pharmacokinetics and pharmacodynamics. Drugs. 1995; 50(2): 222–39.PubMedCrossRefGoogle Scholar
  8. 8.
    Giudicelli JF, Tillement JP. Influence of sex on drug kinetics in man. Clin Pharmacokinet. 1977; 2: 157–66.PubMedCrossRefGoogle Scholar
  9. 9.
    Bonate PL. Gender-related differences in xenobiotic metabolism. J Clin Pharmacol. 1991; 31: 684–90.PubMedGoogle Scholar
  10. 10.
    Food and Drug Administration. Guideline for the study and evaluation of gender differences in the clinical evaluation of drugs. Fed Regist. 1993; 58(139): 39406–16.Google Scholar
  11. 11.
    Merkatz RB, Temple R, Sobel S, et al. Working Group on Women in Clinical Trials (1993). Women in clinical trials of new drugs: a change in Food and Drug Administration policy. N Engl J Med. 1993; 329: 292–6.Google Scholar
  12. 12.
    Shaw RW. Neuroendocrinology of the menstrual cycle in humans. Clin Endocrinol Metab 1978 Nov; 7(3): 531–59.PubMedCrossRefGoogle Scholar
  13. 13.
    Paaby P, Miller-Petersen J, Larsen CE, et al. Endogenous overnight creatinine clearance, serum β2-microglobulin and serum water during the menstrual cycle. Acta Med Scand. 1987; 221: 191–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Nafziger AN, Schwartzman MS, Bertino JS. Absence of tobramycin pharmacokinetic and creatinine clearance variation during the menstrual cycle: implied absence of variation in glomerular filtration rate. J Clin Pharmacol. 1989; 29(8): 757–63.PubMedGoogle Scholar
  15. 15.
    Forsling M, Akerlun DM, Stromberg P. Variations in plasma concentrations of vasopressin during the menstrual cycle. J Endocrinol. 1981; 89: 263–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Katz FH, Romf FTP. Plasma aldosterone and renin activity during the menstrual cycle. J Clin Endocrinol Metab. 1972; 34: 819–23.PubMedCrossRefGoogle Scholar
  17. 17.
    Olson BR, Forman MR, Lanza E, et al. Relation between sodium balance and menstrual cycle symptoms in normal women. Ann Intern Med. 1996; 125: 564–7.PubMedGoogle Scholar
  18. 18.
    Parboosingh J, Doig A, Michie EA. Changes in renal water and electrolyte excretion occurring before and after induced ovulation and their relation to total oestrogen and pregnanediol excretion. J Obstet Gynaecol Br Commonw. 1974; 81(6): 417–22.PubMedCrossRefGoogle Scholar
  19. 19.
    Yeko TR, Rao PS, Parsons AK, et al. Atrial natriuretic peptide, oestradiol and progesterone in women undergoing spontaneous and gonadotrophin-stimulated ovulatory cycles. Hum Reprod. 1995; 10(11): 2872–4.PubMedGoogle Scholar
  20. 20.
    Albano JD, Campbell SK, Farrer A, et al. Gender differences in urinary kallikrein excretion in man: variation throughout the menstrual cycle. Clin Sci. 1994; 86(2): 227–31.PubMedGoogle Scholar
  21. 21.
    Wald A, Van Thiel DH, Hoeschstetter L, et al. Gastrointestinal transit: effect of the menstrual cycle. Gastroenterology. 1981; 80: 1497–500.PubMedGoogle Scholar
  22. 22.
    Mones J, Carrio I, Calabuig R, et al. Influence of the menstrual cycle and of menopause on the gastric emptying rate of solids in female volunteers. Eur J Nucl Med. 1993; 20: 600–2.PubMedCrossRefGoogle Scholar
  23. 23.
    Hsu JJ, Kin CH, O’Connor MK, et al. Effect of menstrual cycle on esophageal emptying of liquid and solid boluses. Mayo Clin Proc. 1993; 68: 753–6.PubMedGoogle Scholar
  24. 24.
    Miller SB, Sita A. Parental history of hypertension, menstrual cycle phase, and cardiovascular response to stress. Psychosom Med. 1994; 56: 61–9.PubMedGoogle Scholar
  25. 25.
    Dunne FP, Barry DG, Ferriss JB, et al. Changes in blood pressure during the normal menstrual cycle. Clin Sci. 1991; 81: 515–8.PubMedGoogle Scholar
  26. 26.
    Durrington PN. Biological variation in serum lipid concentrations. Scand J Clin Lab Invest 1990; 198 Suppl.: 86–91.CrossRefGoogle Scholar
  27. 27.
    Tersman Z, Collins A, Eneroth P. Cardiovascular responses to psychological and physiological Stressors during the menstrual cycle. Psychosom Med. 1991; 53: 185–97.PubMedGoogle Scholar
  28. 28.
    Jern C, Manhem K, Eriksson E, et al. Hemostatic responses to mental stress during the menstrual cycle. Thromb Haemost. 1991; 66: 614–8.PubMedGoogle Scholar
  29. 29.
    Basdevant A, De Lignieres B, Bigorie B, et al. Estradiol, progesterone, and plasma lipids during the menstrual cycle. Diabete Metab. 1981; 7: 1–4.PubMedGoogle Scholar
  30. 30.
    Reed RG, Pearson TA, Stewart PW, et al. Variance in serum lipids and lipoproteins with menstrual cycle in premenopausal women is no greater than variance in postmenopausal women or men. Circulation. 1995; 91: 923.Google Scholar
  31. 31.
    Heiling VJ, Jensen MD. Free fatty acid metabolism in the follicular and luteal phases of the menstrual cycle. J Clin Endocrinol Metab. 1992; 74: 806–10.PubMedCrossRefGoogle Scholar
  32. 32.
    Pansini F, Piccolo R, Bassi P, et al. Basal and forskolin-stimulated cyclic adenosine monophosphate in intact human platelets during the menstrual cycle. Am J Obstet Gynecol. 1986; 154: 679–82.PubMedGoogle Scholar
  33. 33.
    Cederblad G, Hahn L, Korsan-Bengtsen K, et al. Variations in blood coagulation, fibrinolysis, platelet function, and various plasma proteins during the menstrual cycle. Haemostasis. 1977; 6: 294–302.PubMedGoogle Scholar
  34. 34.
    Larsen LF, Andersen HR, Hansen AB, et al. Variation in risk indicators of cardiovascular disease during the menstrual cycle: an investigation of within-subject variation in glutathione peroxidase, homeostatic variables, lipids and lipoproteins in healthy young women. Scand J Clin Lab Invest. 1996; 56: 241–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Mathur S, Mathur RS, Goust JM, et al. Cyclic variations in white cell subpopulations in the human menstrual cycle: correlations with progesterone and estradiol. Clin Immunol Immunopathol. 1979; 13: 246–53.PubMedCrossRefGoogle Scholar
  36. 36.
    Bisdee JT, Garlick PJ, James WPT. Metabolic changes during the menstrual cycle. Br J Nutr. 1989; 61: 641–50.PubMedCrossRefGoogle Scholar
  37. 37.
    Christy NP, Shaver JC. Estrogens and the kidney. Kidney Int. 1974; 6: 366–76.PubMedCrossRefGoogle Scholar
  38. 38.
    Harvey AM, Malvin RL, Vander AJ. Comparison of creatinine secretion in men and women. Nephron. 1966; 3: 201–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Davidson JM, Noble MCB. Serial changes in 24 hour creatinine clearance during normal menstrual cycle and the first trimester of pregnancy. Br J Obstet Gynaecol. 1981; 88: 10–7.CrossRefGoogle Scholar
  40. 40.
    Singer JS, Brandt LJ. Pathophysiology of the gastrointestinal tract during pregnancy. Am J Gastroenterol. 1991; 86: 1695–712.PubMedGoogle Scholar
  41. 41.
    Hutson WR, Roehrkasse RL, Wald A. Influence of gender and menopause on gastric emptying and motility. Gastroenterology. 1989; 96: 11–7.PubMedGoogle Scholar
  42. 42.
    Horowitz M, Maddern J, Chatterton E, et al. The normal menstrual cycle has no effect on gastric emptying. Br J Obstet Gynaecol. 1985; 92: 743–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Thurnbull GK, Thompson DG, Day S, et al. Relationships between symptoms, menstrual cycle and oro-cecal transit in normal and constipated women. Gut. 1989; 30: 30–4.CrossRefGoogle Scholar
  44. 44.
    Sweeting J. Does the time of the month affect the function of the gut? Gastroenterology. 1992; 102: 1084–5.PubMedGoogle Scholar
  45. 45.
    Degen LP, Phillips SE. Variability of gastrointestinal transit in healthy women and men. Gut. 1996; 39: 299–305.PubMedCrossRefGoogle Scholar
  46. 46.
    Little BC, Zahn TR. Changes in mood and autonomic functioning during the menstrual cycle. Psychophysiology. 1974; 11: 579–90.PubMedCrossRefGoogle Scholar
  47. 47.
    Girdler SS, Pedersen CA, Stern RA, et al. The menstrual cycle and premenstrual syndrome: modifiers of cardiovascular reactivity in women. Health Psychol. 1993; 12: 180–92.PubMedCrossRefGoogle Scholar
  48. 48.
    Girdler SS, Kight KC. Hemodynamic stress responses in men and women examined as a function of female menstrual cycle phase. Int J Psychophysiol. 1994; 17: 233–48.PubMedCrossRefGoogle Scholar
  49. 49.
    Kharitonov SA, Logan-Sinclair RB, Bussett CM, et al. Peak expiratory nitric oxide differences in men and women: relation to the menstrual cycle. Br Heart J. 1994; 72: 243–5.PubMedCrossRefGoogle Scholar
  50. 50.
    Kaplan BJ, Whitsett SF, Robinson JW. Menstrual cycle phase is a potential confounder in psychophysiology research. Psychophysiology. 1990; 27: 445–50.PubMedCrossRefGoogle Scholar
  51. 51.
    Karpanou EA, Vyssoulis GP, Georgoudi DG, et al. Disparate serum lipid changes between normotensive and hypertensive women during the menstrual cycle. Am J Cardiol. 1992; 70: 111–3.PubMedCrossRefGoogle Scholar
  52. 52.
    Schijf CPT, Van der Mooren MJ, Doesburg WH, et al. Difference in serum lipids, lipoprotein, sex hormonc binding globulin and testosterone between the follicular and the luteal phase of the menstrual cycle. Acta Endocrinol. 1993; 129: 130–6.PubMedGoogle Scholar
  53. 53.
    Lebech AM, Kjaer A, Lebech PE. Metabolic changes during the normal menstrual cycle: a longitudinal study. Am J Obstet Gynecol. 1990; 163: 414–6.PubMedGoogle Scholar
  54. 54.
    Reed RG, Pearson TA, Stewart PW, et al. Do premenopausal women exhibit significant biologic variability in plasma lipids as a function of menstrual status. Clin Chem 1995; 41; S136.Google Scholar
  55. 55.
    Clark BA, Elahi D, Epstein FH. The influence of gender, age, and the menstrual cycle on plasma atrial natriuretic peptide. J Clin Endocrinol Metab. 1990; 70: 349–52.PubMedCrossRefGoogle Scholar
  56. 56.
    Trigoso WF, Wesly JM, Meranda DL, et al. Vasopressin and atrial natriuretic hormonc response to hypertonic saline during the follicular and luteal phases of the menstrual cycle. Hum Reprod. 1996; 11(11): 2392–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Janowsky DS, Berens SC, Davis JM. Correlations between mood, weight, and electrolytes during the menstrual cycle: a renin-angiotensin-aldosterone hypothesis of premenstrual tension. Psychosom Med. 1973; 325: 143–53.Google Scholar
  58. 58.
    Reeves BD, Garvin JE, McElin TW. Premenstrual tension: symptoms and weight changes related to potassium therapy. Am J Obstet Gynecol. 1971; 109: 1036–41.PubMedGoogle Scholar
  59. 59.
    Dadlani AG, Chandwani S, Desai CA, et al. Serum electrolytes during various phases of menstrual cycle. Indian J Physiol Pharmacol. 1982; 26: 302–6.PubMedGoogle Scholar
  60. 60.
    Stephenson LA, Kolka MA, Wilkerson JF. Metabolic and thermoregulatory responses to exercise in menstrual cycles of athletic and non-athletic women. Med Sci Sports Exerc. 1982; 14: 270–5.PubMedCrossRefGoogle Scholar
  61. 61.
    Williams CL, Stancel GM. Estrogens and progestins. In: Hardman JG, Limbird LE, editors. Goodman & Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1996: 1411–58.Google Scholar
  62. 62.
    Gleichauf CN, Roe DA. The menstrual cycle’s effect on the reliability of bioimpedance measurements for assessing body composition. Am J Clin Nutr. 1989; 50: 903–7.PubMedGoogle Scholar
  63. 63.
    Webb P. 24-hour energy expenditure and the menstrual cycle. Am J Clin Nutr. 1986; 55: 637–40.Google Scholar
  64. 64.
    Nicklas BJ, Hackney AC, Sharp RL, et al. The menstrual cycle and exercise: performance, muscle glycogen, and substrate responses. Int J Sports Med. 1989; 10: 264–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Craft IL, Wise IJ. Changes in amino acid metabolism during the menstrual cycle. J Obstet Gynaecol Br Commonw. 1969; 76: 928–33.PubMedCrossRefGoogle Scholar
  66. 66.
    Toth EL, Suthijumroon A, Crockford PM, et al. Insulin action does not change during the menstrual cycle in normal women. J Clin Endocrinol Metab. 1987; 64: 74–80.PubMedCrossRefGoogle Scholar
  67. 67.
    Harlow SD, Ephross SA. Epidemiology of menstruation and its relevance to women’s health. Epidemiol Rev. 1995; 17(2): 265–86.PubMedGoogle Scholar
  68. 68.
    Ansar Ahmed S, Penhale WJ, Talal N. Sex hormones, immune responses, and autoimmune diseases: mechanism of a sex hormonc action. Am J Pathol. 1985; 121: 531–51.PubMedGoogle Scholar
  69. 69.
    Polan ML, Kuo A, Loukides J, et al. Cultured human luteal peripheral monocytes secrete increased levels of interleukin-1. J Clin Endocrinol Metab. 1990; 70: 480–4.PubMedCrossRefGoogle Scholar
  70. 70.
    Leslie CA, Dubey DP. Increased PGE2 from human monocytes isolated in the luteal phase of the menstrual cycle: implications for immunity? Prostaglandins. 1994; 47: 41–54.PubMedGoogle Scholar
  71. 71.
    Sulke AN, Jones DB, Wood PJ. Variation in natural killer activity in peripheral blood during the menstrual cycle. BMJ (Clin Res Ed). 1985; 290: 884–8.CrossRefGoogle Scholar
  72. 72.
    Moldofsky H, Lue FA, Shahal B, et al. Diurnal sleep/wake-related immune function during the menstrual cycle of healthy young women. J Sleep Res. 1995; 4: 150–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Backstrom T, Jorpes P. Serum phenytoin, phenobarbital, carbamazepine, albumin and plasma estradiol progesterone concentrations during the menstrual cycle in women with epilepsy. Acta Neurol Scand. 1979; 58: 63–71.Google Scholar
  74. 74.
    Boggess KA, Williamson HO, Homm RJ. Influence of the menstrual cycle on systemic diseases. Obstet Gynecol Clin North Am. 1990; 17(2): 321–42.PubMedGoogle Scholar
  75. 75.
    Serrander AM, Peek KE. Changes in contact lens comfort related to the menstrual cycle and menopause: a review of articles. J Am Optom Assoc. 1993; 64(3): 162–6.PubMedGoogle Scholar
  76. 76.
    Dalton K. Influence of menstruation on glaucoma. Br J Ophthalmol. 1967; 51(10): 692–5.PubMedCrossRefGoogle Scholar
  77. 77.
    Qureshi IA. Intraocular pressure: association with menstrual cycle, pregnancy and menopause in apparently healthy women. Chin J Physiol. 1995; 38(4): 229–34.PubMedGoogle Scholar
  78. 78.
    Kalogeromitros D, Katsarou A, Armenaka M, et al. Influence of the menstrual cycle on skin-prick test reactions to histamine, morphine and allergen. Clin Exp Allergy. 1995; 25(5): 461–6.PubMedCrossRefGoogle Scholar
  79. 79.
    Leibenluft E. Women with bipolar illness: clinical and research issues. Am J Psychiatry. 1996; 153: 163–73.PubMedGoogle Scholar
  80. 80.
    Smolensky MH, D’Alonzo GE. Medical chronobiology: concepts and applications. Am Rev Respir Dis 1993; 147(6 Pt 2): S2–19.PubMedGoogle Scholar
  81. 81.
    Gotthardt M, Clark JD, Roy TM. ‘Ovarian asthma’: fact or fancy? J Ky Med Assoc. 1996; 94(3): 105–8.PubMedGoogle Scholar
  82. 82.
    Eliasson O, Scherzer HH, Jr DeGraff AC. Morbidity in asthma in relation to the menstrual cycle. J Allergy Clin Immunol 1986; 77(1 Pt 1): 87–94.PubMedCrossRefGoogle Scholar
  83. 83.
    Gibbs CJ. Coutts II, Lock R, et al. Premenstrual exacerbation of asthma. Thorax. 1984; 39(11): 833–6.Google Scholar
  84. 84.
    Hanley SP. Asthma variation with menstruation. Br J Dis Chest. 1981; 75(3): 306–8.PubMedCrossRefGoogle Scholar
  85. 85.
    Skobeloff EM, Spivey WH, Silverman R, et al. The effect of the menstrual cycle on asthma presentations in the emergency department. Arch Intern Med. 1996; 156(16): 1837–40.PubMedCrossRefGoogle Scholar
  86. 86.
    Pauli BD, Reid RL, Munt PW, et al. Influence of the menstrual cycle on airway function in asthmatic and normal subjects. Am Rev Respir Dis. 1989; 140(20): 358–62.PubMedCrossRefGoogle Scholar
  87. 87.
    Newnham DM, Wheeldon NM, McFarlane LC, et al. Extrapulmonary β2-responses to intravenous salbutamol during the menstrual cycle. Eur J Clin Pharmacol. 1994; 46: 511–5.PubMedCrossRefGoogle Scholar
  88. 88.
    Tan KS, McFarlane LC, Coutie WJ, et al. Effects of exogenous female sex-steroid hormones on lymphocyte beta 2-adrenoceptors in normal females. Br J Clin Pharmacol. 1996; 41(5): 414–6.PubMedCrossRefGoogle Scholar
  89. 89.
    Herkes GK, Eadie MJ. Possible roles for frequent salivary antiepileptic drug monitoring in the management of epilepsy. Epilepsy Res. 1990; 6(2): 146–54.PubMedCrossRefGoogle Scholar
  90. 90.
    Zimmerman AW. Hormones and epilepsy. Neurol Clin. 1986; 4(4): 853–61.PubMedGoogle Scholar
  91. 91.
    Rosciszewska D, Buntner B, Guz I, et al. Ovarian hormones, anticonvulsant drugs, and seizures during the menstrual cycle in women with epilepsy. J Neurol Neurosurg Psychiatry. 1986; 49(1): 47–51.PubMedCrossRefGoogle Scholar
  92. 92.
    Duncan S, Read CL, Brodie MJ. How common is catamenial epilepsy? Epilepsia. 1993; 34(5): 827–31.PubMedCrossRefGoogle Scholar
  93. 93.
    Herkes GK, Eadie MJ, Sharbrough F, et al. Patterns of seizure occurrence in catamenial epilepsy. Epilepsy Res. 1993; 15(1): 47–52.PubMedCrossRefGoogle Scholar
  94. 94.
    Morrell MJ. Hormones and epilepsy through the lifetime. Epilepsia. 1992; 22 Suppl. 4: S49–S61.CrossRefGoogle Scholar
  95. 95.
    Herzog AG. Reproductive endocrine considerations and hormonal therapy for women with epilepsy. Epilepsia. 1991; 32 Suppl. 6: S27–S33.PubMedCrossRefGoogle Scholar
  96. 96.
    Mattson RH, Cramer JA. Epilepsy, sex hormones, and antiepileptic drugs. Epilapsia. 1985; 26 Suppl. 1: S40–S51.CrossRefGoogle Scholar
  97. 97.
    Backstrom T. Epileptic seizures in women related to plasma estrogen and progesterone during the menstrual cycle. Acta Neurol Scand. 1976; 54: 321–47.PubMedCrossRefGoogle Scholar
  98. 98.
    Rodriguez Macias KA. Catamenial epilepsy: gynecological and hormonal implications. Five case reports. Gynecol Endocrinol. 1996; 10(2): 139–42.Google Scholar
  99. 99.
    Jones BM, Jones MK. Alcohol effects in women during the menstrual cycle. Ann NY Acad Sci. 1976; 273: 576–87.PubMedCrossRefGoogle Scholar
  100. 100.
    Lammers SMM, Mainzer DEH, Breteler MHM. Do alcohol pharmacokinetics in women vary due to the menstrual cycle? Addiction. 1995; 90(1): 23–30.PubMedCrossRefGoogle Scholar
  101. 101.
    Miaskiewicz SL, Shively CA, Vesell ES. Sex differences in absorption kinetics of sodium salicylate. Clin Pharmacol Ther. 1982; 31(1): 30–7.PubMedCrossRefGoogle Scholar
  102. 102.
    Jochemsen R, Van der Graaff M, Boeijinga JK, et al. Influence of sex, menstrual cycle and oral contraception on the disposition of nitrazepam. Br J Clin Pharmacol. 1982; 13(3): 319–24.PubMedCrossRefGoogle Scholar
  103. 103.
    Shavit G, Lerman P, Korczyn AD, et al. Phenytoin pharmacokinetics in catamenial epilepsy. Neurology. 1984; 34(7): 959–61.PubMedCrossRefGoogle Scholar
  104. 104.
    Daneshmend TK, Jackson L, Roberts CJC. Physiological and pharmacological variability in estimated hepatic blood flow in man. Br J Clin Pharmacol. 1981; 11: 491–6.PubMedCrossRefGoogle Scholar
  105. 105.
    Somani SM, Khurana RC. Mechanism of estrogen-imipramine interaction. JAMA. 1973; 223: 560.PubMedCrossRefGoogle Scholar
  106. 106.
    Martucci CP, Fishman J. P450 enzymes of estrogen metabolism. Pharmacol Ther. 1993; 57: 237–57.PubMedCrossRefGoogle Scholar
  107. 107.
    Waxman DJ. Interactions of hepatic cytochromes P450 with steroid hormones. Biochem Pharmacol. 1988; 37: 71–84.PubMedCrossRefGoogle Scholar
  108. 108.
    Walle T, Walle UK, Cowart TD, et al. Pathway-selective sex differences in the metabolic clearance of propranolol in human subjects. Clin Pharmacol Ther. 1989; 46: 257–63.PubMedCrossRefGoogle Scholar
  109. 109.
    Miners JO, Atwood J, Birkett DJ. Influence of sex and oral contraceptive steroids on paracetamol metabolism. Br J Clin Pharmacol. 1983; 16: 503–9.PubMedCrossRefGoogle Scholar
  110. 110.
    Riester EF, Pantuck EJ, Pantuck CB, et al. Antipyrine metabolism during the menstrual cycle. J Pharmacol Ther. 1980; 28: 384–91.Google Scholar
  111. 111.
    Kellerman G, Luyten-Kellerman M, Horning MG, et al. Elimination of antipyrine and benzo[a]pyrene metabolism in cultured human lymphocytes. Clin Pharmacol Ther. 1976; 20: 72–80.Google Scholar
  112. 112.
    Bruguerolle B, Toumi M, Fraj F, et al. Influence of menstrual cycle on theophylline pharmacokinetics in asthmatics. Eur J Clin Pharmacol. 1990; 39(1): 59–61.PubMedCrossRefGoogle Scholar
  113. 113.
    Manowitz P, Schull CM. Methaqualone metabolism by rat liver microsomes. Res Commun Chem Pathol Pharmacol. 1976; 13(1): 27–39.PubMedGoogle Scholar
  114. 114.
    Oram M, Wilson K, Burnett D, et al. Metabolic oxidation of methaqualone in extensive and poor metabolisers of debrisoquine. Eur J Clin Pharmacol. 1982; 23(2): 147–50.PubMedCrossRefGoogle Scholar
  115. 115.
    Oram M, Wilson K, Burnett D. The influence of oral contraceptives on the metabolism of methaqualone in man. Br J Clin Pharmacol. 1982; 14(3): 341–5.PubMedCrossRefGoogle Scholar
  116. 116.
    Abdu-Aguye I, Dunlop D, Patel P, et al. Propranolol pharmacokinetics during the menstrual cycle. Postgrad Med J. 1986; 62: 1093–5.PubMedCrossRefGoogle Scholar
  117. 117.
    Gerdin E, Rane A. N-Demethylation of ethylmorphine in pregnant and non-pregnant women and in men: an evaluation of the effects of sex steroids. Br J Clin Pharmacol. 1992; 34: 250–5.PubMedCrossRefGoogle Scholar
  118. 118.
    Zeiner AR, Kegg PS. Menstrual cycle and oral contraceptive effects on alcohol pharmacokinetics in Caucasian females. Curr Alcohol. 1981; 8: 47–56.PubMedGoogle Scholar
  119. 119.
    Miners JO, Atwood J, Birkett DJ. Influence of sex and oral contraceptive steroids on paracetamol metabolism. Br J Clini Pharmacol. 1983; 16: 503–9.CrossRefGoogle Scholar
  120. 120.
    Nayak VK, Kshirsagar NA, Desai KN, et al. Influence of menstrual cycle on antipyrine pharmacokinetics in healthy Indian female volunteers. Br J Clin Pharmacol. 1988; 26(5): 604–6.PubMedCrossRefGoogle Scholar
  121. 121.
    Lane JD, Steege JF, Rupp SL, et al. Menstrual cycle effects on caffeine elimination in the human female. Eur J Clin Pharmacol. 1992; 43: 543–6.PubMedCrossRefGoogle Scholar
  122. 122.
    Wojcicki J, Gawronska-Szklarz B, Kazimierczyk J, et al. Comparative pharmacokinetics of paracetamol in men and women considering follicular and luteal phases. Arzneimittel Forschung. 1979; 29: 350–2.PubMedGoogle Scholar
  123. 123.
    Wilson K, Oram M, Horth C, et al. The influence of the menstrual cycle on the metabolism and clearance of methaqualone. Br J Clin Pharmacol. 1982; 14: 333–9.PubMedCrossRefGoogle Scholar
  124. 124.
    Brick J, Nathan PE, Westrick E, et al. The effect of menstrual cycle on blood alcohol levels and behavior. J Stud Alcohol. 1986; 47: 472–7.PubMedGoogle Scholar
  125. 125.
    Kirkwood C, Moore A, Hayes P, et al. Influence of menstrual cycle and gender on alprazolam pharmacokinetics. Clin Pharmacol Ther. 1991; 50(4): 404–9.PubMedCrossRefGoogle Scholar
  126. 126.
    Greenblatt DJ, Wright CE. Clinical pharmacokinetics of alprazolam: therapeutic implications. Clin Pharmacokinet. 1993; 24(6): 453–71.PubMedCrossRefGoogle Scholar
  127. 127.
    Lew KH, Ludwig EA, Milad MA, et al. Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 1993; 54: 402–14.PubMedCrossRefGoogle Scholar
  128. 128.
    Macdonald JL, Herman RJ, Verbeek RK. Sex-difference and the effects of smoking and oral contraceptive steroids on the kinetics of diflunisal. Eur J Clin Pharmacol. 1990; 38: 175–9.PubMedGoogle Scholar
  129. 129.
    Cordaro JA, Morse GD, Bartos L, et al. Zidovudine pharmacokinetics in HIV-positive women during different phases of the menstrual cycle. Pharmacotherapy. 1993; 13(4): 369–77.PubMedGoogle Scholar
  130. 130.
    Kinney EL, Trautmann J, Gold JA, et al. Underrepresentation of women in new drug trials. Ann Intern Med. 1981; 95: 495–9.PubMedGoogle Scholar
  131. 131.
    Reinberg A, Smolensky M. Circadian changes of drug disposition in man. Clin Pharmacokinet. 1982; 7: 401–20.PubMedCrossRefGoogle Scholar
  132. 132.
    Kawachi I, Colditz GA. Invited commentary: confounding, measurement error, and publication bias in studies of passive smoking. Amer J Epidemiol. 1996; 144(10): 909–15.CrossRefGoogle Scholar

Copyright information

© Adis International Limited 1998

Authors and Affiliations

  1. 1.Clinical Pharmacology Research CenterBassett HealthcareCooperstownUSA
  2. 2.Department of MedicineBassett HealthcareCooperstownUSA

Personalised recommendations