Luteal Development, Ovulation
Conditions
Keywords
Celebrex, prostoglandin inhibitor, ovulation, emergency contraception
Brief summary
The purpose of this study is to assess the effect that Celebrex (a COX-2 inhibitor and non-steroidal anti-inflammatory drug) has on ovulation.
Detailed description
A prospective randomized double-blind crossover study of healthy reproductive-aged (18-35 years old) women with regular cycles, not currently using or needing hormonal contraception, were recruited. Women will undergo ovarian ultrasound and serum hormone monitoring during four menstrual cycles (control cycle, treatment cycle 1, washout cycle, treatment cycle 2). Subjects received study drug (oral celecoxib 400 mg or placebo) either 1) once daily starting on cycle day 8 and continuing until follicle rupture or the onset of next menses if follicle rupture did not occur (pre-LH surge dosing) or 2) once daily beginning with the LH surge and continued for 6 days (post-LH surge dosing). Women will be randomly assigned to one of the above treatment schemes and received the other in the subsequent treatment cycle. This study aims to determine if treatment with a highly selective COX2 inhibitor, celecoxib, would be a more effective agent in terms of causing ovulatory dysfunction. This study also aims to determine whether treatment with celecoxib would adversely affect luteal function.
Interventions
DRUGCelebrex
400 mg PO daily intermittently based on hormone and ultrasound findings
DRUGPlacebo
Placebo identical to celecoxib
Sponsors
Society of Family Planning
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18-35 * Currently NOT using hormonal contraception * Cycle length between 26-34 days * General good health (specifically no hx of: diabetes, cardiac problems, moderate/severe heart burn (GERD), obesity (BMI \> 30), hypertension (BP \> 130/80) * Willing and able to agree to randomization and informed consent * Willing and able to use a menstrual diary to chart bleeding Serum progesterone \> 3 ng/ml (from cycle day 18-25) * Willing and able to return to clinic for bi-weekly for blood tests and ultrasounds throughout cycles 2, 3 & 5
Exclusion criteria
* Diabetes * Cardiac disease * Moderate to severe heart burn (or GERD) Obesity (BMI \> 30) Hypertension (BP \> 130/80) * Allergy to NSAIDS * Currently pregnant or trying to conceive * Polycystic Ovarian Syndrome * Use of hormonal contraception (participants can use barrier methods, spermicide, female or male sterilization, copper intrauterine device, abstinence, or have female partners
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Cycles With Ovulation Dysfunction When Taken After Ovulation: Extended Luteal Phase | 4 cycles (approximately 4 months) | One cycle corresponds to one participant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Hormone Levels | 4 cycles (approximately 4 months) | Average serum levels of progesterone (ng/mL) and luteinizing hormone (ng/mL) normalized to days of the luteal phase of menstrual cycle. |
| Peak Estradiol Level | 4 cycles (approximately 4 months) | Average serum levels of estradiol (pg/mL) normalized to days of the luteal phase of menstrual cycle. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PreLH/postLH Control cycle First, preLH surge dosing of celecoxib and postLH surge dosing of placebo. Followed by, preLH surge dosing of placebo and postLH surge dosing of drug. | 10 |
| PostLH/preLH Control cycle First, postLH surge dosing of celecoxib and preLH surge dosing of placebo. Followed by, postLH surge dosing of placebo and preLH surge dosing of drug. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | PreLH/postLH | PostLH/preLH | Total |
|---|---|---|---|
| Age, Continuous | 26.2 years STANDARD_DEVIATION 5.9 | 28.5 years STANDARD_DEVIATION 4.9 | 27.4 years STANDARD_DEVIATION 5.4 |
| Race/Ethnicity, Customized Non-Hispanic, Caucasian | 9 Participants | 8 Participants | 17 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Number of Cycles With Ovulation Dysfunction When Taken After Ovulation: Extended Luteal Phase
One cycle corresponds to one participant
Time frame: 4 cycles (approximately 4 months)
Population: Placebo treatment was not analyzed. This cycle was purely included in the study flow to keep investigators blinded to treatment allocation. It was pre-specified that it would not be analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Cycle | Number of Cycles With Ovulation Dysfunction When Taken After Ovulation: Extended Luteal Phase | 1 Participants |
| Pre-LH Celecoxib | Number of Cycles With Ovulation Dysfunction When Taken After Ovulation: Extended Luteal Phase | 6 Participants |
| Post-LH Surge Celecoxib | Number of Cycles With Ovulation Dysfunction When Taken After Ovulation: Extended Luteal Phase | 5 Participants |
Secondary
Peak Estradiol Level
Average serum levels of estradiol (pg/mL) normalized to days of the luteal phase of menstrual cycle.
Time frame: 4 cycles (approximately 4 months)
Population: One cycle corresponds to one participant. Placebo treatment was not analyzed. This cycle was purely included in the study flow to keep investigators blinded to treatment allocation. It was pre-specified that it would not be analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Cycle | Peak Estradiol Level | 274 pg/mL | Standard Deviation 99.6 |
| Pre-LH Celecoxib | Peak Estradiol Level | 289.4 pg/mL | Standard Deviation 124.5 |
| Post-LH Surge Celecoxib | Peak Estradiol Level | 282.2 pg/mL | Standard Deviation 106.7 |
Secondary
Peak Hormone Levels
Average serum levels of progesterone (ng/mL) and luteinizing hormone (ng/mL) normalized to days of the luteal phase of menstrual cycle.
Time frame: 4 cycles (approximately 4 months)
Population: One cycle corresponds to one participant. Placebo treatment was not analyzed. This cycle was purely included in the study flow to keep investigators blinded to treatment allocation. It was pre-specified that it would not be analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Cycle | Peak Hormone Levels | LH (luteinizing hormone) | 39.7 ng/mL | Standard Deviation 25 |
| Control Cycle | Peak Hormone Levels | P (progesterone) | 13.3 ng/mL | Standard Deviation 3.3 |
| Pre-LH Celecoxib | Peak Hormone Levels | LH (luteinizing hormone) | 46.2 ng/mL | Standard Deviation 28.4 |
| Pre-LH Celecoxib | Peak Hormone Levels | P (progesterone) | 13.5 ng/mL | Standard Deviation 3.9 |
| Post-LH Surge Celecoxib | Peak Hormone Levels | LH (luteinizing hormone) | 42.6 ng/mL | Standard Deviation 22.2 |
| Post-LH Surge Celecoxib | Peak Hormone Levels | P (progesterone) | 12.3 ng/mL | Standard Deviation 4.7 |