Trial Outcomes & Findings for A Multicenter Study to Evaluate the Effects of a 91-day Oral Contraceptive on Bone Mineral Density in Adolescent Females (NCT NCT00924560)

NCT ID: NCT00924560

Last Updated: 2014-10-22

Results Overview

Bone mineral density was measured by dual energy X-ray absorptiometry (DXA) scan. DXA scans were interpreted centrally by blinded, certified technologists. Percent change from Baseline was calculated as (BMD at Month 12 - BMD at Baseline)/BMD at Baseline \* 100%.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 1361 participants
• Primary outcome timeframe: Baseline and Month 12
• Results posted on: 2014-10-22

Participant Flow

Healthy, postmenarcheal, adolescent females who were either willing to be randomly assigned to 1 of 2 open-label oral contraceptive (OC) treatment regimens or who were not seeking current treatment with hormonal contraceptives and agreed not to use hormonal contraception throughout the 12-month duration of the study (control group).

Eligible participants initiating treatment with OCs were randomly assigned to one of the two treatment groups; eligible participants not initiating treatment with hormonal contraceptives were assigned to the untreated control group. Twenty-six participants at one clinic were excluded from all analyses as the site was closed due to audit findings.

Participant milestones

Measure	91-day Levonorgestrel OC Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control Participants received no oral contraceptives during the study.
Overall Study STARTED	458	448	455
Overall Study Received Treatment	422	411	0
Overall Study COMPLETED	247	240	372
Overall Study NOT COMPLETED	211	208	83

Reasons for withdrawal

Measure	91-day Levonorgestrel OC Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control Participants received no oral contraceptives during the study.
Overall Study Did Not Meet Protocol Requirements	4	2	1
Overall Study Non Compliance with the Protocol	20	15	4
Overall Study Physician Decision	2	3	4
Overall Study Withdrawal by Subject	50	44	18
Overall Study Adverse Event	39	33	0
Overall Study Pregnancy	5	7	1
Overall Study Lost to Follow-up	78	94	45
Overall Study Miscellaneous Reasons	13	10	10

Baseline Characteristics

A Multicenter Study to Evaluate the Effects of a 91-day Oral Contraceptive on Bone Mineral Density in Adolescent Females

Baseline characteristics by cohort

Measure	91-day Levonorgestrel OC n=458 Participants Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=448 Participants Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=455 Participants Participants received no oral contraceptives during the study.	Total n=1361 Participants Total of all reporting groups
Age, Continuous	16.0 years STANDARD_DEVIATION 1.61 • n=5 Participants	15.9 years STANDARD_DEVIATION 1.71 • n=7 Participants	14.8 years STANDARD_DEVIATION 1.72 • n=5 Participants	15.6 years STANDARD_DEVIATION 1.77 • n=4 Participants
Sex: Female, Male Female	458 Participants n=5 Participants	448 Participants n=7 Participants	455 Participants n=5 Participants	1361 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized African-American	87 participants n=5 Participants	87 participants n=7 Participants	72 participants n=5 Participants	246 participants n=4 Participants
Race/Ethnicity, Customized Asian	3 participants n=5 Participants	9 participants n=7 Participants	12 participants n=5 Participants	24 participants n=4 Participants
Race/Ethnicity, Customized Caucasian	251 participants n=5 Participants	265 participants n=7 Participants	255 participants n=5 Participants	771 participants n=4 Participants
Race/Ethnicity, Customized Hispanic	102 participants n=5 Participants	79 participants n=7 Participants	111 participants n=5 Participants	292 participants n=4 Participants
Race/Ethnicity, Customized Other	15 participants n=5 Participants	8 participants n=7 Participants	5 participants n=5 Participants	28 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Month 12

Population: Per-protocol analysis set, including all participants who received at least 1 dose of study treatment (does not apply to Control group), had both Baseline and one post-baseline assessment via DXA, and who completed all procedures at all scheduled study visits including the 12-month DXA scans, and did not have any major protocol violations.

Bone mineral density was measured by dual energy X-ray absorptiometry (DXA) scan. DXA scans were interpreted centrally by blinded, certified technologists.

Percent change from Baseline was calculated as (BMD at Month 12 - BMD at Baseline)/BMD at Baseline * 100%.

Outcome measures

Measure	91-day Levonorgestrel OC n=238 Participants Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=229 Participants Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=362 Participants Participants received no oral contraceptives during the study.
Percent Change From Baseline to 12 Months in Lumbar Spine Bone Mineral Density (BMD)	2.26 percent change Standard Error 0.168	1.45 percent change Standard Error 0.171	2.50 percent change Standard Error 0.139

SECONDARY outcome

Timeframe: Baseline, Month 6 and Month 12

Population: Per-protocol analysis set

Bone mineral density was measured by dual energy X-ray absorptiometry (DXA) scan. DXA scans were interpreted centrally by blinded, certified technologists.

Outcome measures

Measure	91-day Levonorgestrel OC n=238 Participants Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=229 Participants Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=362 Participants Participants received no oral contraceptives during the study.
Change From Baseline in Lumbar Spine Bone Mineral Density Change from Baseline to Month 12	0.02 g/cm^2 Standard Error 0.002	0.01 g/cm^2 Standard Error 0.002	0.03 g/cm^2 Standard Error 0.001
Change From Baseline in Lumbar Spine Bone Mineral Density Change from Baseline to Month 6	0.02 g/cm^2 Standard Error 0.001	0.01 g/cm^2 Standard Error 0.001	0.01 g/cm^2 Standard Error 0.001

SECONDARY outcome

Timeframe: Baseline, Month 6 and Month 12

Population: Per-protocol analysis set

Bone mineral content was measured by dual energy X-ray absorptiometry (DXA) scans and interpreted centrally by blinded, certified technologists.

Outcome measures

Measure	91-day Levonorgestrel OC n=238 Participants Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=229 Participants Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=362 Participants Participants received no oral contraceptives during the study.
Change From Baseline in Lumbar Spine Bone Mineral Content (BMC) Change from Baseline to Month 6	1.29 g Standard Error 0.095	0.69 g Standard Error 0.097	1.12 g Standard Error 0.079
Change From Baseline in Lumbar Spine Bone Mineral Content (BMC) Change from Baseline to Month 12	1.86 g Standard Error 0.120	1.20 g Standard Error 0.122	1.94 g Standard Error 0.099

SECONDARY outcome

Timeframe: Baseline, Month 6 and Month 12

Population: Per-protocol analysis set with available Baseline proximal femur DXA scans; participants with available proximal femur DXA scans at each time point are indicated by "n".

Bone mineral density was measured by dual energy X-ray absorptiometry (DXA) scan. DXA scans were interpreted centrally by blinded, certified technologists.

Outcome measures

Measure	91-day Levonorgestrel OC n=238 Participants Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=228 Participants Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=362 Participants Participants received no oral contraceptives during the study.
Change From Baseline in Proximal Femur Bone Mineral Density Change from Baseline to Month 6 (n=238, 227, 358)	0.01 g/cm^2 Standard Error 0.001	0.00 g/cm^2 Standard Error 0.001	0.01 g/cm^2 Standard Error 0.001
Change From Baseline in Proximal Femur Bone Mineral Density Change from Baseline to Month 12 (n=238, 224, 359)	0.02 g/cm^2 Standard Error 0.002	0.01 g/cm^2 Standard Error 0.002	0.01 g/cm^2 Standard Error 0.001

SECONDARY outcome

Timeframe: Baseline, Month 6 and Month 12

Population: Per-protocol analysis set with available Baseline proximal femur DXA scans; participants with available proximal femur DXA scans at each time point are indicated by "n".

Bone mineral content was measured by dual energy X-ray absorptiometry (DXA) scans and interpreted centrally by blinded, certified technologists.

Outcome measures

Measure	91-day Levonorgestrel OC n=238 Participants Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=228 Participants Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=362 Participants Participants received no oral contraceptives during the study.
Change From Baseline in Proximal Femur Bone Mineral Content (BMC) Change from Baseline to Month 6 (n=238, 227, 358)	0.26 g Standard Error 0.059	0.09 g Standard Error 0.061	0.13 g Standard Error 0.049
Change From Baseline in Proximal Femur Bone Mineral Content (BMC) Change from Baseline to Month 12 (n=238, 224, 359)	0.59 g Standard Error 0.066	0.28 g Standard Error 0.068	0.43 g Standard Error 0.055

SECONDARY outcome

Timeframe: Baseline, Month 6 and Month 12

Population: Per-protocol analysis set with Baseline total body DXA scans. Participants with available total body DXA scans at each time point are indicated by "n".

Bone mineral density was measured by dual energy X-ray absorptiometry (DXA) scan. DXA scans were interpreted centrally by blinded, certified technologists.

Outcome measures

Measure	91-day Levonorgestrel OC n=130 Participants Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=126 Participants Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=150 Participants Participants received no oral contraceptives during the study.
Change From Baseline in Total Body Bone Mineral Density Change from Baseline to Month 6 (n=130, 126, 149)	0.01 g/cm^2 Standard Error 0.001	0.01 g/cm^2 Standard Error 0.001	0.01 g/cm^2 Standard Error 0.001
Change From Baseline in Total Body Bone Mineral Density Change from Baseline to Month 12 (n=130, 126, 150)	0.01 g/cm^2 Standard Error 0.002	0.01 g/cm^2 Standard Error 0.002	0.02 g/cm^2 Standard Error 0.001

SECONDARY outcome

Timeframe: Baseline, Month 6 and Month 12

Population: Per-protocol analysis set with Baseline total body DXA scans. Participants with available total body DXA scans at each time point are indicated by "n".

Bone mineral content was measured by dual energy X-ray absorptiometry (DXA) scans and interpreted centrally by blinded, certified technologists.

Outcome measures

Measure	91-day Levonorgestrel OC n=130 Participants Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=126 Participants Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=150 Participants Participants received no oral contraceptives during the study.
Change From Baseline in Total Body Bone Mineral Content (BMC) Change from Baseline to Month 6 (n=130, 126, 149)	40.77 g Standard Error 6.571	38.70 g Standard Error 6.638	46.26 g Standard Error 6.231
Change From Baseline in Total Body Bone Mineral Content (BMC) Change from Baseline to Month 12 (n=130, 126, 150)	72.86 g Standard Error 8.325	63.78 g Standard Error 8.409	84.95 g Standard Error 7.871

SECONDARY outcome

Timeframe: Baseline, Month 6 and Month 12

Population: Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by "n".

Outcome measures

Measure	91-day Levonorgestrel OC n=238 Participants Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=227 Participants Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=356 Participants Participants received no oral contraceptives during the study.
Change From Baseline in Bone-specific Alkaline Phosphatase Change from Baseline to Month 6 (n=236, 224, 353)	-6.8 µg/L Standard Deviation 8.31	-5.9 µg/L Standard Deviation 7.84	-6.2 µg/L Standard Deviation 10.42
Change From Baseline in Bone-specific Alkaline Phosphatase Change from Baseline to Month 12 (n=235, 225, 347)	-6.9 µg/L Standard Deviation 8.64	-6.6 µg/L Standard Deviation 8.82	-10.3 µg/L Standard Deviation 12.49

SECONDARY outcome

Timeframe: Baseline, Month 6 and Month 12

Population: Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by "n".

Outcome measures

Measure	91-day Levonorgestrel OC n=234 Participants Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=227 Participants Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=350 Participants Participants received no oral contraceptives during the study.
Change From Baseline in Serum Deoxypyridinoline Change from Baseline to Month 6 (n=234, 224, 349)	-0.1 nmol/L Standard Deviation 2.43	-0.1 nmol/L Standard Deviation 1.95	0.1 nmol/L Standard Deviation 2.33
Change From Baseline in Serum Deoxypyridinoline Change from Baseline to Month 12 (n=233, 226, 348)	-0.1 nmol/L Standard Deviation 2.21	0.1 nmol/L Standard Deviation 2.05	-0.1 nmol/L Standard Deviation 2.28

SECONDARY outcome

Timeframe: Baseline, Month 6 and Month 12

Population: Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by "n".

Outcome measures

Measure	91-day Levonorgestrel OC n=238 Participants Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=227 Participants Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=357 Participants Participants received no oral contraceptives during the study.
Change From Baseline in Serum Osteocalcin Change from Baseline to Month 6 (n=236, 224, 354)	-4.8 nmol/L Standard Deviation 7.00	-3.9 nmol/L Standard Deviation 6.74	-5.1 nmol/L Standard Deviation 11.94
Change From Baseline in Serum Osteocalcin Change from Baseline to Month 12 (n=235, 225, 348)	-4.5 nmol/L Standard Deviation 6.69	-3.7 nmol/L Standard Deviation 7.19	-7.1 nmol/L Standard Deviation 11.74

SECONDARY outcome

Timeframe: Baseline, Month 6 and Month 12

Population: Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by "n".

Outcome measures

Measure	91-day Levonorgestrel OC n=238 Participants Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=227 Participants Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=356 Participants Participants received no oral contraceptives during the study.
Change From Baseline in Serum Procollagen 1 N-terminal Propeptide Change from Baseline to Month 6 (n=237, 225, 355)	-49.9 µg/L Standard Deviation 58.55	-38.7 µg/L Standard Deviation 51.14	-57.8 µg/L Standard Deviation 92.58
Change From Baseline in Serum Procollagen 1 N-terminal Propeptide Change from Baseline to Month 12 (n=235, 226, 349)	-50.4 µg/L Standard Deviation 60.20	-39.8 µg/L Standard Deviation 55.73	-86.0 µg/L Standard Deviation 118.69

SECONDARY outcome

Timeframe: Baseline, Month 6 and Month 12

Population: Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by "n".

Outcome measures

Measure	91-day Levonorgestrel OC n=237 Participants Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=227 Participants Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=357 Participants Participants received no oral contraceptives during the study.
Change From Baseline in Serum Type I Collagen N-telopeptide Change from Baseline to Month 6 (n=235, 224, 356)	-4.8 nM bone collagen equivalents (BCE) Standard Deviation 9.69	-3.9 nM bone collagen equivalents (BCE) Standard Deviation 10.68	-0.7 nM bone collagen equivalents (BCE) Standard Deviation 13.60
Change From Baseline in Serum Type I Collagen N-telopeptide Change from Baseline to Month 12 (n=236, 225, 350)	-4.5 nM bone collagen equivalents (BCE) Standard Deviation 10.22	-4.3 nM bone collagen equivalents (BCE) Standard Deviation 10.71	-3.1 nM bone collagen equivalents (BCE) Standard Deviation 12.64

SECONDARY outcome

Timeframe: 12 months

Population: The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.

An adverse event was any untoward medical occurrence in a clinical investigation subject participating in the clinical study, and did not necessarily need to have a causal relationship with treatment or the clinical study. The relationship of each adverse event to study treatment or procedures, and the severity and seriousness of each adverse event was judged by the investigator, as described below.

A severe AE is defined as incapacitating, with inability to perform usual activities.

A serious adverse event is an adverse event occurring at any dose that resulted in any of the following outcomes or actions:

• fatal or life-threatening;
• required or prolonged inpatient hospitalization;
• resulted in persistent or significant disability/incapacity;
• congenital anomaly or birth defect;
• important medical event.

Outcome measures

Measure	91-day Levonorgestrel OC n=421 Participants Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=412 Participants Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=437 Participants Participants received no oral contraceptives during the study.
Number of Participants With Adverse Events (AEs) Any adverse event	252 participants	258 participants	274 participants
Number of Participants With Adverse Events (AEs) Severe adverse event	14 participants	20 participants	10 participants
Number of Participants With Adverse Events (AEs) Treat-related adverse event	100 participants	95 participants	7 participants
Number of Participants With Adverse Events (AEs) Deaths	0 participants	0 participants	0 participants
Number of Participants With Adverse Events (AEs) Other serious adverse events	9 participants	12 participants	0 participants
Number of Participants With Adverse Events (AEs) Withdrawn from study due to adverse events	34 participants	33 participants	1 participants

Adverse Events

91-day Levonorgestrel OC

Serious events: 9 serious events

Other events: 156 other events

Deaths: 0 deaths

28-day Levonorgestrel OC

Serious events: 12 serious events

Other events: 160 other events

Deaths: 0 deaths

Untreated Control

Serious events: 0 serious events

Other events: 196 other events

Deaths: 0 deaths

Serious adverse events

Measure	91-day Levonorgestrel OC n=421 participants at risk Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=412 participants at risk Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets (containing 100 μg LNG/20 μg EE) followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=437 participants at risk Participants received no oral contraceptives during the study.
Cardiac disorders Wolff-Parkinson-White syndrome	0.00% 0/421 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
General disorders Serositis	0.00% 0/421 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Infections and infestations Appendicitis	0.48% 2/421 • Number of events 2 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Infections and infestations Clostridial infection	0.00% 0/421 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 2 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Infections and infestations Hepatitis infectious mononucleosis	0.24% 1/421 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/412 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Infections and infestations Pyelonephritis	0.24% 1/421 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/412 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Infections and infestations Urinary tract infection	0.24% 1/421 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/412 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Injury, poisoning and procedural complications Injury	0.24% 1/421 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/412 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Injury, poisoning and procedural complications Post concussion syndrome	0.00% 0/421 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Injury, poisoning and procedural complications Road traffic accident	0.24% 1/421 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/412 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Musculoskeletal and connective tissue disorders Back pain	0.24% 1/421 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/412 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Musculoskeletal and connective tissue disorders Knee deformity	0.00% 0/421 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Nervous system disorders Dizziness	0.24% 1/421 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/412 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Pregnancy, puerperium and perinatal conditions Abortion incomplete	0.00% 0/421 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/421 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.00% 0/421 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Psychiatric disorders Affective disorder	0.00% 0/421 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Psychiatric disorders Depression	0.00% 0/421 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Psychiatric disorders Drug abuse	0.00% 0/421 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Psychiatric disorders Drug dependence	0.00% 0/421 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Psychiatric disorders Major depression	0.00% 0/421 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Psychiatric disorders Suicide attempt	0.24% 1/421 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/412 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Renal and urinary disorders Calculus ureteric	0.24% 1/421 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/412 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Renal and urinary disorders Hydronephrosis	0.00% 0/421 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.24% 1/412 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.24% 1/421 • Number of events 1 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/412 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.

Other adverse events

Measure	91-day Levonorgestrel OC n=421 participants at risk Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).	28-day Levonorgestrel OC n=412 participants at risk Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets (containing 100 μg LNG/20 μg EE) followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).	Untreated Control n=437 participants at risk Participants received no oral contraceptives during the study.
Gastrointestinal disorders Nausea	4.3% 18/421 • Number of events 20 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	6.1% 25/412 • Number of events 28 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	3.2% 14/437 • Number of events 15 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Infections and infestations Nasopharyngitis	8.3% 35/421 • Number of events 46 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	12.6% 52/412 • Number of events 62 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	12.1% 53/437 • Number of events 91 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Infections and infestations Upper respiratory tract infection	7.1% 30/421 • Number of events 44 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	6.6% 27/412 • Number of events 32 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	12.1% 53/437 • Number of events 79 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Musculoskeletal and connective tissue disorders Arthralgia	2.1% 9/421 • Number of events 17 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	3.4% 14/412 • Number of events 26 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	5.0% 22/437 • Number of events 26 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Nervous system disorders Headache	15.4% 65/421 • Number of events 124 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	16.7% 69/412 • Number of events 120 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	20.1% 88/437 • Number of events 197 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Reproductive system and breast disorders Dysmenorrhoea	4.8% 20/421 • Number of events 31 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	6.3% 26/412 • Number of events 41 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	8.5% 37/437 • Number of events 88 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Reproductive system and breast disorders Metrorrhagia	6.9% 29/421 • Number of events 40 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	3.4% 14/412 • Number of events 21 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	0.00% 0/437 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.3% 14/421 • Number of events 16 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	2.4% 10/412 • Number of events 12 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.	6.9% 30/437 • Number of events 35 • 12 months The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 215-591-3000

Email: ustevatrials@tevapharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
• Publication restrictions are in place

Restriction type: OTHER