Progestin Contraceptives for Birth Control Effects

Overseen By Women's Health Research Unit Research Unit Department of OB/Gyn

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: Oregon Health and Science University

Must not be taking: NSAIDs, Anticoagulants, P450 inducers

Disqualifiers: Uterine pathology, Abnormal bleeding, Pregnancy, others

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

Compensation: Varies

Number of Visits: 4

Duration: 12 months

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how progestin contraception affects menstrual bleeding patterns. Participants will choose between a contraceptive implant, such as the Etonogestrel implant, or an injectable, such as DMPA (Depo-Provera), and researchers will monitor changes in their menstrual cycles over a year. The study will examine the uterine lining to determine the causes of different bleeding patterns. Individuals with regular menstrual cycles and no recent use of hormonal contraceptives might be suitable for this study. As an Early Phase 1 trial, this research focuses on understanding how these contraceptive methods work in people, offering participants a chance to contribute to foundational knowledge.

Will I have to stop taking my current medications?

The trial requires that you stop using hormonal contraceptives and certain other medications before enrolling. Specifically, you must not have used oral hormonal contraceptives for at least one month, implantable contraceptives for at least two months, or injectable hormonal contraceptives for the past nine months. Additionally, you should not be using NSAIDs regularly or any anticoagulants.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Depo-Provera (DMPA) is a safe birth control option for many women. More than 3 million women have used DMPA, and studies, including those by the World Health Organization, have confirmed its safety. However, it should not be used for more than two years unless other methods are unsuitable.

For the Etonogestrel implant, research indicates it is a very effective and safe birth control method. The most common side effect is a change in menstrual bleeding patterns, affecting about one in ten women and possibly leading some to stop using the implant.

Both methods are well-known in birth control and have been used by many people. Always consult a healthcare provider about any concerns to find the best option for your needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about DMPA (depot medroxyprogesterone acetate) and the Etonogestrel implant because they offer unique approaches to birth control. DMPA is administered as an injection every three months, providing a long-lasting and discreet option compared to daily oral contraceptives. The Etonogestrel implant, on the other hand, is a tiny rod inserted under the skin that releases hormones over three years, offering a convenient, long-term solution without the need for frequent doctor visits or daily attention. Both treatments provide highly effective, low-maintenance alternatives to traditional methods like oral contraceptives and barrier methods, empowering users with more choices for managing their reproductive health.

What evidence suggests that this trial's treatments could be effective for birth control?

This trial will compare the effectiveness of DMPA (Depo-Provera) and the etonogestrel implant (Nexplanon) as birth control methods. Research has shown that DMPA has a pregnancy rate of less than 1% with perfect use and about 4% with typical use, demonstrating its effectiveness when used correctly. The etonogestrel implant is even more effective, with over 99% effectiveness, making it one of the most reliable options available. The implant releases hormones that prevent the release of eggs from the ovaries, while DMPA also uses hormones to prevent pregnancy. Both options offer long-term protection and have been widely used, providing strong confidence in their effectiveness. ^{3 6 7 8 9}

Who Is on the Research Team?

Alison B Edelman, MD, MPH

Principal Investigator

Oregon Health and Science University

Are You a Good Fit for This Trial?

This trial is for women aged 18-40 with regular menstrual cycles, a BMI of 19-35, and no contraindications to DMPA or hormonal implants. They shouldn't be pregnant, breastfeeding, or planning pregnancy during the study; have used certain contraceptives recently; have uterine pathology; fall under CDC's category 3/4 for contraceptive use; smoke heavily; or take specific medications regularly.

Inclusion Criteria

I can safely use birth control shots or implants.

Regular menstrual cycles (25-35 day cycle length with bleeding 8 days or less)

Body Mass Index of 19-35

Exclusion Criteria

Centers for Disease Control Medical Eligibility for Contraceptive use category 3 or 4 for contraceptive usage

I have experienced unusual bleeding from my uterus.

Chronic use of cigarettes (More than 1 cigarette per week)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the contraceptive implant (Nexplanon) or the contraceptive injectable (Depo-Provera) for up to 12 months, with 4 endometrial biopsies, blood draws, physical exams, and pregnancy tests

12 months

4 visits for biopsies, regular visits for blood draws and exams

Follow-up

Participants are monitored for safety and effectiveness after treatment, including the analysis of bleeding patterns and endometrial profiling

6 months

What Are the Treatments Tested in This Trial?

Interventions

• DMPA
• Etonogestrel implant

Trial Overview The study examines how progestin contraception (Nexplanon implant or Depo-Provera injection) affects menstrual changes by analyzing endometrial biopsies and blood samples over a year. Participants will also track their bleeding patterns daily via text or email.

How Is the Trial Designed?

Group I: DMPA Active Control 1 Intervention

Group II: Etonogestrel implant Active Control 1 Intervention

DMPA is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Depo-Provera for:

• Contraception
• Endometriosis
• Renal carcinoma
• Cushing's syndrome

Approved in European Union as Depo-Provera for:

• Contraception
• Endometriosis
• Renal carcinoma
• Cushing's syndrome

Approved in Canada as Depo-Provera for:

• Contraception
• Endometriosis
• Renal carcinoma
• Cushing's syndrome

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

Over a 10-year period, 5433 adverse effects (AEs) were reported for the etonogestrel contraceptive implant, with only 7% classified as serious, indicating that while AEs are common, they are mostly not severe.

The introduction of Nexplanon® has significantly reduced complications related to insertion and migration of the implant, highlighting improvements in safety and efficacy compared to its predecessor, Implanon®.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety profile of etonogestrel contraceptive implant (Nexplanon&#174; and Implanon&#174;) reported in France]. Simon, C., Agier, MS., Béné, J., et al.[2017]

The subdermal contraceptive implant etonogestrel (Implanon) primarily prevents pregnancy by inhibiting ovulation, while also causing complex changes in the endometrium, such as alterations in histology and menstrual bleeding patterns.

Current research is exploring how etonogestrel affects endometrial functions, including vascular and angiogenic processes, which may contribute to breakthrough bleeding experienced by some users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endometrial effects of etonogestrel (Implanon) contraceptive implant. Varma, R., Mascarenhas, L.[2021]

In a study of 89 women undergoing medical abortion, the addition of a progestin-based contraceptive (either an etonogestrel implant or DMPA injection) on the same day as mifepristone did not affect the high success rate of the procedure, which was 98%.

This success rate is comparable to previous findings where medical abortion was performed without the concurrent administration of progestin contraceptives, indicating that the use of these contraceptives is safe and does not compromise the effectiveness of medical abortion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progestin-based contraceptive on the same day as medical abortion. Park, J., Robinson, N., Wessels, U., et al.[2018]

In a national pharmacovigilance study in France, 39 unintended pregnancies were reported among users of the Implanon contraceptive implant, primarily due to insertion technique errors (77% of cases).

The study highlights the importance of proper training for healthcare providers in the insertion of Implanon to prevent complications, as issues with insertion can lead to migration of the implant and difficulties in removal, potentially requiring invasive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Insertion problems, removal problems, and contraception failures with Implanon]. Bensouda-Grimaldi, L., Jonville-Béra, AP., Beau-Salinas, F., et al.[2014]

Progestin-only contraceptives (POCs) like pills, injections, IUDs, and implants are effective first-line options for preventing unwanted pregnancies, offering various advantages and disadvantages that need to be communicated to users.

Clinicians play a crucial role in ensuring women are well-informed about potential side effects and benefits of POCs, which can enhance adherence and reduce the likelihood of discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Considerations for the use of progestin-only contraceptives. Freeman, S., Shulman, LP.[2022]

Nexplanon® is a long-acting contraceptive implant that is generally considered safe, but it can occasionally cause moderate to severe adverse reactions.

A specific case of delayed-type hypersensitivity reaction to Nexplanon® was reported, which resolved after the implant was removed, highlighting the importance of monitoring for potential allergic reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed-type hypersensitivity reaction against Nexplanon®. Serati, M., Bogani, G., Kumar, S., et al.[2014]

In a study of 385 high-risk women, those using the intrauterine device (IUD) had lower rates of discontinuation compared to those using depo-medroxyprogesterone acetate (DMPA), with 18.8% of IUD users discontinuing versus 67.0% of DMPA users.

While women using DMPA were initially found to have a higher likelihood of subsequent sexually transmitted diseases (STDs), this association diminished when accounting for other factors, suggesting that the choice of contraceptive may be influenced by sexual risk factors rather than inherent safety differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term, reversible contraception use among high-risk women treated in a university-based gynecology clinic: comparison between IUD and depo-provera. Cropsey, KL., Matthews, C., Campbel, S., et al.[2022]

The study involving 18 HIV-negative women found that the use of the etonogestrel Implant (Eng-Implant) was associated with a moderate increase in the availability of HIV target cells (CCR5+CD4+ T cells) in the genital tract, but the activation of these cells did not increase, suggesting no clear elevation in HIV risk.

Overall immune responses showed minimal changes after implant placement, indicating that while there are some shifts in HIV target cell populations, it remains uncertain whether these changes significantly affect the risk of acquiring HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of etonogestrel implant use on T-cell and cytokine profiles in the female genital tract and blood. Haddad, LB., Swaims-Kohlmeier, A., Mehta, CC., et al.[2020]

Progestin-only contraception methods, such as implants and injections, are highly effective and have few contraindications, making them safe options for long-term birth control.

While both methods can cause changes in menstrual bleeding patterns and potential bone mineral density loss, these effects are generally reversible, and there is no significant increased risk of cancer associated with their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contraception Update: Progestin-Only Implants and Injections. Deshmukh, P., Antell, K., Brown, EJ.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7533104/

An Evidence-Based Update on Contraception The failure rate is less than 1% with perfect use and 4% with typical use. In addition to the aforementioned progestin mechanisms of action, DMPA also affects ...

2. kff.org kff.org/womens-health-policy/dmpa-contraceptive-injection-use-and-coverage/

DMPA Contraceptive Injection: Use and Coverage The DMPA shot has a typical use failure rate of 4% when used once every 12 weeks or three months. ... Condoms or another non-hormonal ...

3. cdc.gov cdc.gov/contraception/hcp/usspr/injectables.html

Injectables | Contraception Approximately four out of 100 DMPA users will become pregnant in the first year with typical use. DMPA is reversible and can be used by patients ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0010782403001367

a highly effective contraceptive option with proven long ... DMPA is a highly effective, convenient nondaily hormonal contraceptive option that has been available worldwide for over 30 years and in the US for the past 10 ...

5. acog.org acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/06/depot-medroxyprogesterone-acetate-and-bone-effects

Depot Medroxyprogesterone Acetate and Bone Effects Depot medroxyprogesterone acetate is a highly effective contraceptive that affords privacy (similar to an intrauterine system) and has a convenient dose ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2004/20246s025lbl.pdf

Depo-Provera Contraceptive Injection (CI) - accessdata.fda.gov The risk of hypospadias (five to eight per 1,000 male births in the general population) may be approximately doubled with exposure to these drugs. There are ...

7. mayoclinic.org mayoclinic.org/tests-procedures/depo-provera/about/pac-20392204

Depo-Provera (birth control shot) Depo-Provera is a birth control shot that has the hormone progestin. Depo-Provera is a well-known brand name for medroxyprogesterone acetate.

8. labeling.pfizer.com labeling.pfizer.com/showlabeling.aspx?id=522

Highlights of prescribing information: Depo-Provera ... The use of Depo-Provera CI is not recommended as a long-term (i.e., longer than 2 years) birth control method unless other options are considered inadequate.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7804881/

Injectable Depot Medroxy Progesterone Acetate: A Safe ... ... DMPA.[4]. Safety and effectiveness. DMPA is a safe contraceptive. Studies by World Health Organization (WHO) on over 3 million woman months of DMPA use give ...