ContraceptionPhase 3NCT03106454
Ovulation Incidence in Oral Contraceptive Users
A Phase 3 study testing Ethinyl Estradiol, Norethindrone acetate, ferrous fumarate and Norethindrone in people with Contraception and Ovulation, run by University of Southern California at 1 site in United States.
Trial summary
Since the introduction of the combined hormonal contraceptive pill, dosages of ethinyl estradiol (EE) have steadily decreased from more than 150mcg to 20mcg in an attempt to improve the risk profile associated with the COC. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraception, Ovulation
- What is being tested?
- Ethinyl Estradiol, Norethindrone acetate, ferrous fumarate and Norethindrone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2014to 1 Jan 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Reproductive aged women 18-45 years old.
- Menstrual cycle length 25-35days
- BMI less than or equal to 40
- English or Spanish speaking
Who cannot join
- Pregnant or breastfeeding in the previous 3 months.
- Use of OC, hormonal vaginal rings or patches, levonorgestrel containing intrauterine device, or etonogestrel implant in the previous 1 month. No use of depot medroxyprogesterone acetate (DMPA) injection in the previous 6 months and at least one menses since discontinuation.
- Medical contraindications to estrogen or progestin use. Specifically: smoking among participants over 35 years old, migraines with aura, history of blood clots, ischemic heart disease, stroke, breast cancer, cervical cancer, liver disease, symptomatic gallbladder disease, uncontrolled hypertension, antiphospholipid antibody syndrome, hyperlipidemia, diabetes with end organ damage (retinopathy, nephropathy, neuropathy) or diagnosis >20 years ago, organ transplant
- Desire to become pregnant in the next 4 months
Trial locations and contacts
1 site in 1 country.
About this study
Since the introduction of the combined hormonal contraceptive pill, dosages of ethinyl estradiol (EE) have steadily decreased from more than 150mcg to 20mcg in an attempt to improve the risk profile associated with the COC. In 2010, the Food and Drug Administration approved a oral contraceptive pill containing EE 10mcg/NET acetate 1mg (Tradename Lo loestrin). However, no studies have compared this formulation to pills containing either higher doses of estrogen or progestin alone. It is not known whether EE 10mcg is sufficient to prevent follicular development or to support the endometrium as well as higher doses of EE. This trial addresses the question of whether an oral contraceptive pill with EE 10mcg/Norethindrone acetate 1mg will better suppress ovulation or have a better side effect profile than a progestin only pill with a nearly equal dose of norethindrone.
Read the detailed description
Use of combined hormonal contraceptives (CHC) containing estrogen is associated with venous thromboembolic events. In an effort to decrease the risks of estrogen, the dose of ethinyl estradiol (EE) contained in combined oral contraceptive (COC) pills has decrease substantially from >100mcg to 20mcg. In 2012, a COC with only 10mcg of EE (Tradename LoLoestrin) was approved by the Food and Drug Administration. However, no studies have compared this formulation to pills containing progestin alone to determine if this very low dose of EE decreases ovulation or improves unscheduled uterine bleeding beyond what is seen with a progestin only pill (POP).
We aim to compare a COC with EE 10mcg/norethindrone (NET) acetate 1mg to a POP containing a nearly equal amount of progestin (norethindrone 1.05mg). The objective of the study is to compare the incidence of ovulation among users of a COC with only EE10mcg/NET acetate 1mg to users of a POP with a nearly identical progestin dose of NET 1.05mg. We plan to recruit 58 women between the ages of 18 and 45 years old, who are ovulatory at baseline based on serum progesterone levels. Subjects will be randomized to take either a COC containing EE 10mcg/NET acetate 1mg or a POP containing NET 1.05mg for one month. During the month of study treatment, we will measure ovulation incidence using a single serum progesterone levels of >=4.0ng/dl, sperm penetration of cervical mucus using the Eggert Kruse classification system, pill compliance by NET serum levels, and side effects including unscheduled uterine bleeding via subject daily diaries.
Our primary outcome, ovulation incidence, will be compared between study arms. Secondary outcomes will compare cervical mucus quality, sperm penetration of cervical mucus, side effects (including uterine bleeding), and pill compliance between users of these two pills.
- Conditions
- Contraception, Ovulation
- Being tested
- Ethinyl Estradiol, Norethindrone acetate, ferrous fumarate, Norethindrone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ethinyl Estradiol, Norethindrone acetate, ferrous fumarateDrug
Also called Loestrin
Combination Oral Contraceptive Pill. Ethinyl Estradiol 10mcg/Norethindrone acetate 1mg/ferrous fumarate 75mg
NorethindroneDrug
Also called Micronor, Camilla
Norethindrone 1.05mg
| Study group | Role | What they receive |
|---|---|---|
| Combination oral contraceptive pill | Active comparator | Ethinyl Estradiol 10mcg/Norethindrone acetate 1mg/ferrous fumarate 75mg Taken cyclically as 24 tablets containing EE 10mcg/NET acetate 1mg 2 tablets of EE 10mcg only 2 tablets of ferrous fumarate 75mg Receives: Drug: Ethinyl Estradiol, Norethindrone acetate, ferrous fumarate |
| Progestin only pill | Experimental | Norethindrone 0.35mg Marketed use for 1 tablet per day. For study dosing, patients will take 3 tablets daily for a total of 1.05mg daily. Receives: Drug: Norethindrone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ovulation
Ovulation based on a single serum progesterone level of 4ng/dl or greater
Measured: A single 28 day cycle
Secondary outcomes (4)
Sperm penetration of cervical mucus
The average distance sperm will travel in vitro in a test tube of cervical mucus collected from the participant.
Measured: A single 28 day cycle
Cervical mucus quality
Scoring of the ovulatory quality (thickness, cellularity, etc.) of cervical mucus collected from the participant
Measured: A single 28 day cycle
Side effects
Side effects self reported by the participant
Measured: A single 28 day cycle
Uterine bleeding
A daily calendar counting the number of days of uterine bleeding participants experience during the study cycle.
Measured: A single 28 day cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2017
- Study startAug 2014
- Primary completionJan 2024
- Study completion1 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ContraceptionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- Society of Family Planning
- Responsible party
- Principal investigator, Brian T. Nguyen, MD MSc, University of Southern California
- Investigators
- Brian T Nguyen, MD, MSc, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03106454
- Sponsor's protocol ID
- HS-09-00669
- Status last verified
- Dec 2025
- First submitted
- 4 Apr 2017
- Last updated
- 26 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ovulation Incidence in Oral Contraceptive Users
- ClinicalTrials.gov ID
- NCT03106454
- Acronym / sponsor ID
- HS-09-00669
- Conditions
- Contraception, Ovulation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- Society of Family Planning
- Study start
- Aug 2014 (actual)
- Primary completion
- Jan 2024 (actual)
- Study completion
- 1 Jan 2024 (actual)
- First posted
- 10 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Since the introduction of the combined hormonal contraceptive pill, dosages of ethinyl estradiol (EE) have steadily decreased from more than 150mcg to 20mcg in an attempt to improve the risk profile associated with the COC. In 2010, the Food and Drug Administration approved a oral contraceptive pill containing EE 10mcg/NET acetate 1mg (Tradename Lo loestrin). However, no studies have compared this formulation to pills containing either higher doses of estrogen or progestin alone. It is not known whether EE 10mcg is sufficient to prevent follicular development or to support the endometrium as well as higher doses of EE. This trial addresses the question of whether an oral contraceptive pill with EE 10mcg/Norethindrone acetate 1mg will better suppress ovulation or have a better side effect profile than a progestin only pill with a nearly equal dose of norethindrone.
Detailed description
Use of combined hormonal contraceptives (CHC) containing estrogen is associated with venous thromboembolic events. In an effort to decrease the risks of estrogen, the dose of ethinyl estradiol (EE) contained in combined oral contraceptive (COC) pills has decrease substantially from >100mcg to 20mcg. In 2012, a COC with only 10mcg of EE (Tradename LoLoestrin) was approved by the Food and Drug Administration. However, no studies have compared this formulation to pills containing progestin alone to determine if this very low dose of EE decreases ovulation or improves unscheduled uterine bleeding beyond what is seen with a progestin only pill (POP).
We aim to compare a COC with EE 10mcg/norethindrone (NET) acetate 1mg to a POP containing a nearly equal amount of progestin (norethindrone 1.05mg). The objective of the study is to compare the incidence of ovulation among users of a COC with only EE10mcg/NET acetate 1mg to users of a POP with a nearly identical progestin dose of NET 1.05mg. We plan to recruit 58 women between the ages of 18 and 45 years old, who are ovulatory at baseline based on serum progesterone levels. Subjects will be randomized to take either a COC containing EE 10mcg/NET acetate 1mg or a POP containing NET 1.05mg for one month. During the month of study treatment, we will measure ovulation incidence using a single serum progesterone levels of >=4.0ng/dl, sperm penetration of cervical mucus using the Eggert Kruse classification system, pill compliance by NET serum levels, and side effects including unscheduled uterine bleeding via subject daily diaries.
Our primary outcome, ovulation incidence, will be compared between study arms. Secondary outcomes will compare cervical mucus quality, sperm penetration of cervical mucus, side effects (including uterine bleeding), and pill compliance between users of these two pills.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Combination oral contraceptive pill | Active comparator | Drug: Ethinyl Estradiol, Norethindrone acetate, ferrous fumarateEthinyl Estradiol 10mcg/Norethindrone acetate 1mg/ferrous fumarate 75mg Taken cyclically as 24 tablets containing EE 10mcg/NET acetate 1mg 2 tablets of EE 10mcg only 2 tablets of ferrous fumarate 75mg |
| Progestin only pill | Experimental | Drug: NorethindroneNorethindrone 0.35mg Marketed use for 1 tablet per day. For study dosing, patients will take 3 tablets daily for a total of 1.05mg daily. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Reproductive aged women 18-45 years old.
- Menstrual cycle length 25-35days
- BMI less than or equal to 40
- English or Spanish speaking
Key exclusion criteria (4 listed)
- Pregnant or breastfeeding in the previous 3 months.
- Use of OC, hormonal vaginal rings or patches, levonorgestrel containing intrauterine device, or etonogestrel implant in the previous 1 month. No use of depot medroxyprogesterone acetate (DMPA) injection in the previous 6 months and at least one menses since discontinuation.
- Medical contraindications to estrogen or progestin use. Specifically: smoking among participants over 35 years old, migraines with aura, history of blood clots, ischemic heart disease, stroke, breast cancer, cervical cancer, liver disease, symptomatic gallbladder disease, uncontrolled hypertension, antiphospholipid antibody syndrome, hyperlipidemia, diabetes with end organ damage (retinopathy, nephropathy, neuropathy) or diagnosis >20 years ago, organ transplant
- Desire to become pregnant in the next 4 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ethinyl Estradiol, Norethindrone acetate, ferrous fumarateAlso: LoestrinCombination Oral Contraceptive Pill. Ethinyl Estradiol 10mcg/Norethindrone acetate 1mg/ferrous fumarate 75mg | Drug | Combination oral contraceptive pill |
| NorethindroneAlso: Micronor, CamillaNorethindrone 1.05mg | Drug | Progestin only pill |
Primary outcome
Ovulation
Time frame: A single 28 day cycle
Ovulation based on a single serum progesterone level of 4ng/dl or greater
4 secondary outcomes
Sperm penetration of cervical mucus
Time frame: A single 28 day cycle
Cervical mucus quality
Time frame: A single 28 day cycle
Side effects
Time frame: A single 28 day cycle
Uterine bleeding
Time frame: A single 28 day cycle
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian T Nguyen, MD, MSc principal investigator
University of Southern California
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ethinyl Estradiol, Norethindrone acetate, ferrous fumarate and Norethindrone in people with Contraception and Ovulation, run by University of Southern California at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ovulation (time frame: A single 28 day cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2025.