title: Effect of oral administration of a continuous 18 day regimen of meloxicam on ovulation: experience of a randomized controlled trial.
abstract: BACKGROUND
  Cyclooxygenase-2 (COX-2) is expressed in all female reproductive organs. Therefore, inhibitors of COX-2 may affect reproductive function. We evaluated the effect of extended administration of meloxicam on ovulation and the menstrual cycle. Our hypothesis was that meloxicam administered from menstrual cycle day 5- 22 could interfere with follicular rupture, without disrupting the menstrual cycle, and could be a potential non-hormonal contraceptive method.
  
  
  METHODS
  The study was conducted in 56 healthy sterilized women. Before the onset of treatment and after the end of treatment, participants were observed during a control cycle to ensure that they had progesterone (P₄) serum levels (>12 nmol/l) consistent with ovulation. Participants were treated for 18 days, during three consecutive cycles. They were randomized to 15 or 30 mg/day. The menstrual cycle was monitored with serial ultrasound and hormone assays in blood.
  
  
  RESULTS
  Fifty-six volunteers completed the study. In 55% of cycles treated with 15 mg/day and in 78% of cycles treated with 30 mg/day (p<0.001) we observed dysfunctional ovulation defined as follicular rupture not preceded 24-48 h earlier by an LH peak or preceded by a blunted LH peak (<21 IU/l) or not followed by an elevated serum P₄ level >12 nmol/l. Ovulation was observed in 44.6% and in 21.7% of women in the lower dose group and the higher dose group, respectively. There were no differences between the two doses in other parameters measured. There were no serious adverse events and adverse events were not different between doses or between control and treated cycles.
  
  
  CONCLUSIONS
  Although administration of meloxicam on menstrual cycle days 5- 22 resulted in a dose-dependent inhibition of ovulation, more than 20% of subjects had normal ovulation with the highest dose.
  
  
  CONCLUSIONS
  Previous studies have shown that oral meloxicam can delay follicle rupture. This study investigated daily oral meloxicam as a non-hormonal contraceptive. Since ovulation occurs in over 20% of cycles even with a high dose of 30 mg daily, it is not likely that the approach would be a highly effective contraceptive strategy.
authors.affiliation: Instituto Chileno de Medicina Reproductiva (ICMER), José Victorino Lastarria 29, apt. 101, Santiago, Santiago, Chile, 8320165; Instituto de Investigaciones Materno Infantil (IDIMI), Faculty of Medicine Universidad de Chile, Santa Rosa 1234, Santiago, Santiago, Chile, 8360160. Electronic address: cjesam@icmer.org.
authors.forename: C
authors.initials: C
authors.lastname: Jesam
authors.affiliation: Instituto Chileno de Medicina Reproductiva (ICMER), José Victorino Lastarria 29, apt. 101, Santiago, Santiago, Chile, 8320165.
authors.forename: A M
authors.initials: AM
authors.lastname: Salvatierra
authors.affiliation: CONRAD/Eastern Virginia Medical School, 1911 Fort Myer Drive (Suite 900), Arlington, VA 22209.
authors.forename: J L
authors.initials: JL
authors.lastname: Schwartz
authors.affiliation: Instituto de Investigaciones Materno Infantil (IDIMI), Faculty of Medicine Universidad de Chile, Santa Rosa 1234, Santiago, Santiago, Chile, 8360160.
authors.forename: A
authors.initials: A
authors.lastname: Fuentes
authors.affiliation: Faculty of Medicine, Universidad Andrés Bello, Echaurren 283, Santiago, Santiago, Chile 8370071El 17-04-2014, a las 13:45.
authors.forename: H B
authors.initials: HB
authors.lastname: Croxatto
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D002677:Chile; D003276:Contraceptives, Oral / Q000008:administration & dosage* / Q000009:adverse effects; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D000077239:Meloxicam; D008597:Menstrual Cycle / Q000097:blood / Q000187:drug effects; D010053:Ovary / Q000000981:diagnostic imaging / Q000187:drug effects; D010060:Ovulation / Q000187:drug effects*; D011374:Progesterone / Q000097:blood; D013843:Thiazines / Q000008:administration & dosage* / Q000009:adverse effects; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D014463:Ultrasonography
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003276:Contraceptives, Oral; D052246:Cyclooxygenase 2 Inhibitors; D013843:Thiazines; D013844:Thiazoles; D011374:Progesterone; D007986:Luteinizing Hormone; D000077239:Meloxicam
keywords: Delayed ovulation; Female contraception; LUF; NSAIDs; Ovarian cycle