Literature DB >> 19631786

Impact of obesity on oral contraceptive pharmacokinetics and hypothalamic-pituitary-ovarian activity.

Alison B Edelman1, Nichole E Carlson, Ganesh Cherala, Myrna Y Munar, Richard L Stouffer, Judy L Cameron, Frank Z Stanczyk, Jeffrey T Jensen.   

Abstract

BACKGROUND: This study was conducted to determine whether increased body mass index (BMI) affects oral contraceptive (OC) pharmacokinetics and suppression of hypothalamic-pituitary-ovarian (HPO) axis activity. STUDY
DESIGN: Ovulatory reproductive-age women with normal weight (BMI <25 kg/m(2); n=10) and with obesity (BMI >30 kg/m(2); n=10) received OCs for two cycles (prospective cohort). Subjects were admitted for two 48-h inpatient stays at the beginning and end of the hormone-free interval. Ethinyl estradiol and levonorgestrel (LNG) levels were evaluated during both inpatient stays. Gonadotropin pulsatility (follicle-stimulating hormone and luteinizing hormone) was measured during the second inpatient stay. Estradiol (E(2)) and progesterone (P) were measured daily during inpatient stays and twice per week in Cycle 2.
RESULTS: BMI was greater in the obese compared to the normal-BMI group [37.3 kg/m(2) (SD, 6.0) vs. 21.9 kg/m(2) (SD, 1.6); p<.05]. The LNG half-life was significantly longer in the obese group (52.1+/-29.4 vs. 25.6+/-9.3 h, p<.05), which correlated with a lower maximum LNG concentration on Cycle 2, Day 1 [1.9 ng/mL (SD, 0.5) vs. 2.5 ng/mL (SD, 0.7)] and a longer time to reach steady state (10 vs. 5 days) in obese women. There were no significant differences in volume of distribution between groups. LH pulse parameters did not differ statistically between groups but trended toward greater HPO activity in the obese group. Additionally, more obese (6/10 vs. 3/10 normal BMI, p>.05) women exhibited E(2) levels consistent with development of a dominant follicle and P levels consistent with ovulation (2/10 vs. 1/10) during Cycle 2.
CONCLUSIONS: Compared to women with normal BMI, obese women exhibit differences in OC pharmacokinetics that are associated with greater HPO activity.

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Year:  2009        PMID: 19631786      PMCID: PMC2736633          DOI: 10.1016/j.contraception.2009.04.011

Source DB:  PubMed          Journal:  Contraception        ISSN: 0010-7824            Impact factor:   3.375


  19 in total

1.  Radioimmunoassay of serum d-norgestrel in women following oral and intravaginal administration.

Authors:  F Z Stanczyk; M Hiroi; U Goebelsmann; P F Brenner; M E Lumkin; D R Mishell
Journal:  Contraception       Date:  1975-09       Impact factor: 3.375

Review 2.  Pharmacokinetics of gestagens: some problems.

Authors:  K Fotherby
Journal:  Am J Obstet Gynecol       Date:  1990-07       Impact factor: 8.661

3.  Deconvolution analysis of hormone data.

Authors:  J D Veldhuis; M L Johnson
Journal:  Methods Enzymol       Date:  1992       Impact factor: 1.600

4.  Oral contraceptives and individual variability of circulating levels of ethinyl estradiol and progestins.

Authors:  Joseph W Goldzieher; Frank Z Stanczyk
Journal:  Contraception       Date:  2008-06-02       Impact factor: 3.375

Review 5.  Pharmacokinetic considerations in obesity.

Authors:  R A Blouin; G W Warren
Journal:  J Pharm Sci       Date:  1999-01       Impact factor: 3.534

6.  Pituitary and ovarian function in women receiving hormonal contraception.

Authors:  B L Cohen; M Katz
Journal:  Contraception       Date:  1979-11       Impact factor: 3.375

7.  Defective expression of cytochrome P450 proteins in the liver of the genetically obese Zucker rat.

Authors:  A Irizar; C R Barnett; P R Flatt; C Ioannides
Journal:  Eur J Pharmacol       Date:  1995-12-07       Impact factor: 4.432

8.  Body weight and risk of oral contraceptive failure.

Authors:  Victoria L Holt; Kara L Cushing-Haugen; Janet R Daling
Journal:  Obstet Gynecol       Date:  2002-05       Impact factor: 7.661

9.  Single- and multiple-dose pharmacokinetics of a low-dose oral contraceptive in women with chronic renal failure undergoing peritoneal dialysis.

Authors:  T M Price; R E Dupuis; B R Carr; F Z Stanczyk; R A Lobo; W Droegemueller
Journal:  Am J Obstet Gynecol       Date:  1993-05       Impact factor: 8.661

Review 10.  Levonorgestrel. Clinical pharmacokinetics.

Authors:  K Fotherby
Journal:  Clin Pharmacokinet       Date:  1995-03       Impact factor: 6.447

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  34 in total

Review 1.  Contraception and the obese woman.

Authors:  Elizabeth Reifsnider; Nonie Mendias; Yolanda Davila; Jennie Bever Babendure
Journal:  J Am Assoc Nurse Pract       Date:  2013-02-27       Impact factor: 1.165

2.  Pharmacokinetics of a combined oral contraceptive in obese and normal-weight women.

Authors:  Carolyn L Westhoff; Anupama H Torgal; Elizabeth R Mayeda; Malcolm C Pike; Frank Z Stanczyk
Journal:  Contraception       Date:  2010-02-20       Impact factor: 3.375

3.  Hormonal contraceptive use before and after conception in relation to preterm birth and small for gestational age: an observational cohort study.

Authors:  E T Jensen; J L Daniels; T Stürmer; W R Robinson; C J Williams; K Vejrup; P Magnus; M P Longnecker
Journal:  BJOG       Date:  2014-10-16       Impact factor: 6.531

4.  Levonorgestrel butanoate intramuscular injection does not reliably suppress ovulation for 90 days in obese and normal-BMI women: a pilot study.

Authors:  Alison B Edelman; Ganesh Cherala; Hong Li; Francis Pau; Diana L Blithe; Jeffrey T Jensen
Journal:  Contraception       Date:  2016-07-27       Impact factor: 3.375

Review 5.  Perspectives on variability in pharmacokinetics of an oral contraceptive product.

Authors:  William J Jusko
Journal:  Contraception       Date:  2016-07-27       Impact factor: 3.375

6.  Effects of ritonavir-boosted protease inhibitors on combined oral contraceptive pharmacokinetics and pharmacodynamics in HIV-positive women.

Authors:  Teresa Barcellos; Melissa Natavio; Frank Z Stanczyk; Dandan Luo; William J Jusko; Nicole M Bender
Journal:  Contraception       Date:  2019-06-10       Impact factor: 3.375

Review 7.  Obesity and hormonal contraceptive efficacy.

Authors:  Jennifer A Robinson; Anne E Burke
Journal:  Womens Health (Lond)       Date:  2013-09

8.  Prolonged monitoring of ethinyl estradiol and levonorgestrel levels confirms an altered pharmacokinetic profile in obese oral contraceptives users.

Authors:  Alison B Edelman; Ganesh Cherala; Myrna Y Munar; Barent Dubois; Martha McInnis; Frank Z Stanczyk; Jeffrey T Jensen
Journal:  Contraception       Date:  2012-11-12       Impact factor: 3.375

9.  Effect of a combined estrogen and progesterone oral contraceptive on circulating adipocytokines adiponectin, resistin and DLK-1 in normal and obese female rhesus monkeys.

Authors:  Kate A Shaw; Jon D Hennebold; Alison B Edelman
Journal:  Contraception       Date:  2012-12-04       Impact factor: 3.375

Review 10.  The creeping Pearl: Why has the rate of contraceptive failure increased in clinical trials of combined hormonal contraceptive pills?

Authors:  James Trussell; David Portman
Journal:  Contraception       Date:  2013-04-11       Impact factor: 3.375

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