title: Transdermal contraception and the renin-angiotensin-aldosterone system in premenopausal women.
abstract: The oral contraceptive pill (OCP) activates the renin-angiotensin-aldosterone system (RAAS) through first-pass hepatic metabolism. Although usually benign, RAAS activation may have detrimental effects on renal and hemodynamic function in some women. Since combined hormonal contraception with the transdermal patch (EVRA) does not undergo first-pass hepatic metabolism, we hypothesized that the RAAS response would be different from that of OCP subjects. Thirty-five nonsmoking, premenopausal women (15 control subjects, 10 OCP subjects, and 10 contraceptive patch subjects) without evidence of cardiovascular disease, renal disease, or diabetes were studied. Baseline angiotensinogen, renin, angiotensin II, aldosterone, and plasma renin activity were assessed along with hormonal and hemodynamic responses to simulated orthostatic stress using incremental lower body negative pressure (LBNP; -15, -25, and -40 mmHg). Baseline levels of angiotensinogen, angiotensin II, and plasma renin activity were significantly higher in OCP subjects compared with normotensive control and contraceptive patch subjects (P < 0.05), whereas aldosterone was significantly higher in OCP versus control subjects only (P < 0.05). Plasma renin levels were significantly lower at baseline in contraceptive patch subjects compared with normotensive control and OCP subjects (P < 0.05). In response to LBNP, increases in renin, angiotensin II, and aldosterone were attenuated in contraceptive patch subjects in conjunction with an exaggerated decline in mean arterial pressure (P < 0.05 vs. control and OCP subjects). The contraceptive patch in healthy premenopausal women is associated with an impaired ability to maintain blood pressure in response to LBNP, possibly due to insensitivity of the endogenous RAAS. Further evaluation may be beneficial in women with kidney disease.
authors.affiliation: Division of Nephrology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada;
authors.forename: Ayodele
authors.initials: A
authors.lastname: Odutayo
authors.affiliation: University Health Network, University of Toronto, Toronto, Ontario, Canada;
authors.forename: David
authors.initials: D
authors.lastname: Cherney
authors.affiliation: University Health Network, University of Toronto, Toronto, Ontario, Canada;
authors.forename: Judith
authors.initials: J
authors.lastname: Miller
authors.affiliation: University of Calgary, Calgary, Alberta, Canada;
authors.forename: Sofia B
authors.initials: SB
authors.lastname: Ahmed
authors.affiliation: University Health Network, University of Toronto, Toronto, Ontario, Canada;
authors.forename: Vesta
authors.initials: V
authors.lastname: Lai
authors.affiliation: Department of Family and Community Medicine, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada; and.
authors.forename: Sheila
authors.initials: S
authors.lastname: Dunn
authors.affiliation: University Health Network, University of Toronto, Toronto, Ontario, Canada;
authors.forename: Nicole
authors.initials: N
authors.lastname: Pun
authors.affiliation: The Institute for Clinical Evaluative Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rahim
authors.initials: R
authors.lastname: Moineddin
authors.affiliation: Division of Nephrology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; University Health Network, University of Toronto, Toronto, Ontario, Canada; michelle.hladunewich@sunnybrook.ca.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Hladunewich
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000804:Angiotensin II / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D016022:Case-Control Studies; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D017697:Premenopause / Q000187:drug effects; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D055815:Young Adult
chemical_list: D003271:Contraceptive Agents, Female; D000804:Angiotensin II; D012083:Renin
keywords: contraceptive patch; oral contraception; renin-angiotensin-aldosterone system