Birth Control Pills and DNA Interaction

Recruiting at 2 trial locations

Overseen By Aaron Lazorwitz, MD, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Yale University

Must be taking: Oral contraceptives

Must not be taking: CYP3A inducers/inhibitors

Disqualifiers: Liver disease, Breast cancer, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 months

700 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop taking medications and supplements known to affect CYP3A, such as rifampin, carbamazepine, ketoconazole, and St. John's wort, during the study.

What data supports the effectiveness of the drug Desogestrel / Ethinyl Estradiol Pill?

A clinical trial with 1,159 women showed that the drug, containing 150 micrograms of desogestrel and 30 micrograms of ethinyl estradiol, was highly effective as a birth control pill, with good cycle control and fewer minor complaints compared to a non-treated cycle. ^{1 2 3 4 5}

Is the Desogestrel/Ethinyl Estradiol pill safe for human use?

The Desogestrel/Ethinyl Estradiol pill has been shown to be generally safe in humans, with studies indicating no serious side effects and good cycle control. It does not cause genetic damage or significant adverse effects on health markers like blood pressure and body weight. ^{1 2 6 7 8}

How does the drug Desogestrel / Ethinyl Estradiol differ from other birth control options?

Desogestrel / Ethinyl Estradiol is unique because it combines a potent progestogen, desogestrel, which lacks androgenic activity (does not cause male-like effects), with ethinyl estradiol, providing effective birth control with good cycle control and fewer minor complaints compared to non-treated cycles. ^{1 6 9 10 11}

What is the purpose of this trial?

The goal of this clinical trial is to evaluate how differences in specific parts of our DNA can influence how individual bodies break down the hormones contained within oral contraceptive pills, which could affect how well these birth control pills work to prevent pregnancy. The investigators are also interested in exploring how these differences in our DNA can also explain why patients taking the exact same formulation of birth control pill will experience very different side effects. The main questions it aims to answer are: * Do individuals with the CYP3A7\*1C variant have increased metabolism of both desogestrel and ethinyl estradiol when taking a combined oral contraceptive pill? * Do individuals with the CYP3A7\*1C variant experience higher rates of breakthrough ovulation while taking a desogestrel/ethinyl estradiol combined oral contraceptive pill? * What novel genetic loci are associated with alterations in steroid hormone pharmacokinetics and pharmacodynamics among a larger cohort of combined oral contraceptive pill users? Participants will take a specific formulation of combined oral contraceptive pill (desogestrel/ethinyl estradiol) and undergo the following procedures: * Blood draw to measure the amount of progestin and estrogen in their system from the combined oral contraceptive pill * Questionnaires to assess side effects possibly caused by the combined oral contraceptive pill * Blood draw to measure endogenous hormone levels and biomarkers that may be affected by the combined oral contraceptive pill * A transvaginal ultrasound to measure any ovarian follicles (optional procedure)

Research Team

Aaron M Lazorwitz, MD, PhD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for individuals using a specific birth control pill (desogestrel/ethinyl estradiol). It's focused on how genetic differences affect the body's processing of these hormones and their effectiveness in preventing pregnancy. Participants will have blood tests, answer questionnaires about side effects, and may opt for an ultrasound to check ovarian follicles.

Inclusion Criteria

Body-mass index ≥18.5kg/m2

Normal blood pressure measurement at study screening

Negative urine pregnancy test at study screening

Exclusion Criteria

Use of injectable contraceptive method within 6 months or current use of an ENG implant

Childbirth within 6 months

History of complicated solid organ transplantation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are administered a combined oral contraceptive pill containing desogestrel and ethinyl estradiol for at least one cycle (21 days) and up to 13 total cycles (one year)

12 months

Monthly visits for blood draws and questionnaires

Follow-up

Participants are monitored for safety and effectiveness after treatment, including optional transvaginal ultrasound and repeated blood draws

4 weeks

1-2 visits (in-person)

Treatment Details

Interventions

• Desogestrel / Ethinyl Estradiol Pill

Trial Overview The study is testing how the CYP3A7*1C gene variant affects metabolism of hormones in oral contraceptives and if it leads to more cases of breakthrough ovulation. It also seeks new genetic factors that influence hormone levels among users of these pills.

Participant Groups

Group I: Combined oral contraceptive pill users Experimental Treatment 1 Intervention

Administered a combined oral contraceptive pill containing desogestrel and ethinyl estradiol (Desogen, 0.15mg desogestrel and 0.03mg ethinyl estradiol per active pill) for at least one cycle (21 days) and up to 13 total cycles (one year)

Desogestrel / Ethinyl Estradiol Pill is already approved in United States, European Union for the following indications:

Approved in United States as Desogen for:

• Prevention of pregnancy

Approved in European Union as Desogen for:

• Prevention of pregnancy

Approved in United States as Kariva for:

• Prevention of pregnancy

Approved in United States as Reclipsen for:

• Prevention of pregnancy

Approved in United States as Azurette for:

• Prevention of pregnancy

Approved in United States as Cyclessa for:

• Prevention of pregnancy

Approved in United States as Isibloom for:

• Prevention of pregnancy

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Findings from Research

The clinical trial with 1,159 women demonstrated that an oral contraceptive containing 150 micrograms of desogestrel and 30 micrograms of ethinyl estradiol is highly effective for preventing pregnancy over 15,222 observed cycles.

The contraceptive showed good cycle control with no serious side effects reported, and minor complaints were less frequent compared to cycles without treatment, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial of an oral contraceptive containing desogestrel and ethinyl estradiol. Weijers, MJ.[2013]

Desogestrel 75 micrograms/day demonstrated superior contraceptive efficacy compared to levonorgestrel 30 micrograms/day, with a Pearl index of 0.14 versus 1.17, indicating fewer pregnancies among users.

Both contraceptive methods had similar safety profiles and overall acceptability, but desogestrel users experienced a more varied bleeding pattern, including higher rates of amenorrhea and infrequent bleeding, especially at the start of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind study comparing the contraceptive efficacy, acceptability and safety of two progestogen-only pills containing desogestrel 75 micrograms/day or levonorgestrel 30 micrograms/day. Collaborative Study Group on the Desogestrel-containing Progestogen-only Pill. [2019]

In a study of 350 contraceptive implant users, self-reported race and ethnicity were found to be strong indicators of genetically determined ancestry, suggesting that these social factors are important in understanding progestin-related side effects.

The analysis revealed no significant associations between genetically determined ancestry or self-reported race/ethnicity and serum etonogestrel concentrations, indicating that these factors do not affect the pharmacokinetics of the contraceptive implant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applicability of ancestral genotyping in pharmacogenomic research with hormonal contraception. Lazorwitz, A., Aquilante, CL., Shortt, JA., et al.[2022]

Mothers taking combined oral contraceptives can safely breast-feed, as the concentrations of hormones like levonorgestrel and ethinylestradiol in breast milk are low.

Newer progestogens such as desogestrel, gestodene, and norgestimate show good bioavailability, but their effectiveness can be influenced by factors like sex hormone binding globulin (SHBG) levels and interactions with other medications, which may affect contraceptive efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of contraceptive steroids. An update. Shenfield, GM., Griffin, JM.[2018]

The desogestrel-only pill Cerazette effectively inhibits ovulation even when taken up to 12 hours late, with only 1% of the 103 women in the study experiencing ovulation during treatment.

Return to ovulation after stopping Cerazette takes at least 7 days, highlighting its reliability as a contraceptive method compared to traditional progestagen-only pills.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance of ovulation inhibition with the 75-microg desogestrel-only contraceptive pill (Cerazette) after scheduled 12-h delays in tablet intake. Korver, T., Klipping, C., Heger-Mahn, D., et al.[2013]

A study involving 43 healthy women taking different types of low-dose oral contraceptive pills for 12 menstrual cycles found no significant increase in chromosomal aberrations or sister chromatid exchange compared to a control group.

The three types of oral contraceptives tested (desogestrel, norgestrel, and gestodene) did not show any statistically significant differences in their genotoxic effects, suggesting they are safe in terms of chromosomal integrity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of genetic damage in human lymphocytes of women using oral contraceptives. Mahrous, HS.[2020]

The study involving 1,221 women over 11,656 cycles showed that the oral contraceptive containing 150 micrograms of desogestrel and 30 micrograms of ethinyl estradiol was highly effective, with no pregnancies due to method failure.

The contraceptive was well tolerated, with less than 2% of participants discontinuing due to bleeding irregularities, and it showed no adverse effects on cervical health, blood pressure, or body weight, indicating its safety and acceptability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter efficacy and safety study of an oral contraceptive containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol. Walling, M.[2019]

New generation oral contraceptives like desogestrel and gestodene are similarly effective in preventing pregnancy and managing menstrual cycles, while also offering a better metabolic profile compared to older contraceptives.

Desogestrel-containing contraceptives have shown effectiveness in treating mild to moderate acne and hirsutism, and their varying estrogen doses allow for personalized treatment options based on individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Classification and comparison of oral contraceptives containing new generation progestogens. Newton, JR.[2019]

Drospirenone and ethinylestradiol, components of common oral contraceptives, were found to cause DNA damage in human breast cells and female mouse bone marrow cells, indicating potential genotoxic effects.

The study revealed that the combination of these two drugs increased DNA damage, suggesting that long-term use of these contraceptives may elevate the risk of cancer development in women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotoxic effects of drospirenone and ethinylestradiol in human breast cells (in vitro) and bone marrow cells of female mice (in vivo). Mir, AH., Dumka, VK., Sultan, F., et al.[2022]

Desogestrel, combined with ethinyl estradiol in the oral contraceptive Marvelon, demonstrated a low use-effectiveness rate of 0.58 Pearl Units across 4074 cycles involving 219 women, indicating its reliability as a contraceptive method.

The study reported no serious side effects associated with the contraceptive, and the drug-related discontinuation rate was relatively low at 12.8% over six months, suggesting good tolerability among users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with an ethinyl estradiol-desogestrel oral contraceptive. Van Trappen, Y., Duvivier, P., Thiery, M., et al.[2013]

Oral contraceptive steroids can have significant drug interactions, where certain medications, especially enzyme-inducing anticonvulsants like phenobarbital and rifampicin, can reduce the effectiveness of contraceptives, potentially leading to breakthrough bleeding or unintended pregnancy.

Conversely, some substances like ascorbic acid and paracetamol can increase blood levels of ethinylestradiol, the active component in many oral contraceptives, which may affect contraceptive efficacy, particularly in women taking high doses of these drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic drug interactions with oral contraceptives. Back, DJ., Orme, ML.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical trial of an oral contraceptive containing desogestrel and ethinyl estradiol. [2013]

2. England pubmed.ncbi.nlm.nih.gov

A double-blind study comparing the contraceptive efficacy, acceptability and safety of two progestogen-only pills containing desogestrel 75 micrograms/day or levonorgestrel 30 micrograms/day. Collaborative Study Group on the Desogestrel-containing Progestogen-only Pill. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Applicability of ancestral genotyping in pharmacogenomic research with hormonal contraception. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of contraceptive steroids. An update. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Maintenance of ovulation inhibition with the 75-microg desogestrel-only contraceptive pill (Cerazette) after scheduled 12-h delays in tablet intake. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Evaluation of genetic damage in human lymphocytes of women using oral contraceptives. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

A multicenter efficacy and safety study of an oral contraceptive containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Classification and comparison of oral contraceptives containing new generation progestogens. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Genotoxic effects of drospirenone and ethinylestradiol in human breast cells (in vitro) and bone marrow cells of female mice (in vivo). [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Clinical experience with an ethinyl estradiol-desogestrel oral contraceptive. [2013]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetic drug interactions with oral contraceptives. [2018]