Medroxyprogesterone acetate and estradiol cypionate injectable suspension (Cyclofem) monthly contraceptive injection: steady-state pharmacokinetics

Contraception. 2013 Jun;87(6):738-43. doi: 10.1016/j.contraception.2012.11.010. Epub 2012 Dec 22.

Abstract

Background: Cyclofem is a combined injectable contraceptive, containing medroxyprogesterone acetate (MPA) and estradiol cypionate. The objective was to characterize the steady-state pharmacokinetics (PK) using tandem liquid chromatography/mass spectrometry and compare these data to a previous PK study of this formulation in US women.

Study design: Fifteen ovulatory, surgically sterile women received three Cyclofem injections, once every 28 days, with serum PK measurements on 23 separate days. Trough levels of estradiol and MPA were obtained on Days 1, 29 and 57, prior to each of the three injections. Steady-state concentrations of MPA and estradiol were assessed during the third treatment month on Days 58, 60, 62, 64, 67, 69, 71, 75, 78 and 85. MPA and serum progesterone levels were measured during the follow-up phase to assess MPA clearance (Days 92, 99, 106, 113, 120, 127, 134 and 141) and return of ovulation (Days 103, 106, 131 and 134).

Results: In the steady state, mean serum MPA concentrations peaked at 1.31 ng/mL at 4.1 days. Mean estradiol levels peaked at 254 pg/mL by 3.3 days. Ovulation was suppressed for at least 77 days post third injection in all but one woman.

Conclusions: Once monthly injections of Cyclofem resulted in contraceptive levels of MPA without accumulation of hormones, consistent with a previous US study.

Trial registration: ClinicalTrials.gov NCT01699022.

Publication types

  • Clinical Trial, Phase I
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biological Availability
  • Contraceptive Agents, Female / administration & dosage
  • Contraceptive Agents, Female / blood
  • Contraceptive Agents, Female / pharmacokinetics*
  • Contraceptive Agents, Female / pharmacology
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / analysis
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Drug Combinations
  • Drugs, Investigational / administration & dosage
  • Drugs, Investigational / analysis
  • Drugs, Investigational / pharmacokinetics*
  • Drugs, Investigational / pharmacology
  • Estradiol / administration & dosage
  • Estradiol / analogs & derivatives*
  • Estradiol / blood
  • Estradiol / metabolism
  • Estradiol / pharmacokinetics
  • Estradiol / pharmacology
  • Female
  • Follow-Up Studies
  • Half-Life
  • Humans
  • Injections, Intramuscular
  • Medroxyprogesterone Acetate / administration & dosage
  • Medroxyprogesterone Acetate / blood
  • Medroxyprogesterone Acetate / pharmacokinetics*
  • Medroxyprogesterone Acetate / pharmacology
  • Metabolic Clearance Rate
  • Ovary / drug effects
  • Ovary / metabolism
  • Ovulation Inhibition / drug effects
  • Suspensions

Substances

  • Contraceptive Agents, Female
  • Delayed-Action Preparations
  • Drug Combinations
  • Drugs, Investigational
  • Suspensions
  • Estradiol
  • CycloProvera
  • estradiol 17 beta-cypionate
  • Medroxyprogesterone Acetate

Associated data

  • ClinicalTrials.gov/NCT01699022