Vaginal Progesterone for Vaginal Atrophy

Overseen By Wendy L Wolfman, MD, FRCSC

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Mount Sinai Hospital, Canada

Must not be taking: Hormone replacement therapy

Disqualifiers: Breast cancer, Tumor, Thrombophlebitis, Kidney, Liver, others

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

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether vaginal progesterone can effectively treat vaginal atrophy, a condition common in post-menopausal women that causes vaginal dryness and irritation. Researchers aim to determine if progesterone serves as a viable alternative to traditional estrogen treatments, particularly for women who cannot use or do not respond to estrogen. Participants will receive either a progesterone suppository or a placebo (a dummy treatment with no active ingredients) to compare results. Women who have experienced vaginal dryness, irritation, soreness, or painful intercourse might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

If you are using any hormone replacement therapy, you will need to stop and complete a washout period before joining the study. The washout period is eight weeks for oral estrogen or progestin, four weeks for transdermal or local vaginal hormones, and eight weeks for progestin-containing intrauterine systems. Non-hormonal therapies like vaginal moisturizers cannot be used during the study, but vaginal lubricants for intercourse are allowed.

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

Research has shown that vaginal progesterone has been safely used in various medical situations. For instance, it has been tested in over 800 women undergoing fertility treatments. These studies found that progesterone is generally well-tolerated, with few serious side effects.

In a related study, women using progesterone vaginal inserts for fertility found the treatment safe and well-tolerated. Some common side effects were minor, such as irritation or discomfort, but they were not severe.

While this study focuses on using progesterone for treating vaginal atrophy, existing safety evidence from its use in other conditions suggests it could be safe in this new context. However, since this trial is in an early phase, ongoing research will provide more detailed safety information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for vaginal atrophy, which often include estrogen therapies, vaginal progesterone offers a unique approach by using a different hormone. Researchers are excited about this treatment because progesterone is known for its anti-inflammatory properties, which might provide relief with potentially fewer side effects associated with estrogen. Additionally, the use of a suppository form allows direct application to the affected area, which could enhance effectiveness and provide targeted relief. This approach could offer a promising alternative for those who cannot use estrogen-based therapies.

What evidence suggests that vaginal progesterone might be an effective treatment for atrophic vaginitis?

Research has shown that vaginal progesterone, which participants in this trial may receive, is effective in other treatments, particularly in reducing the risk of early birth. Studies have found it can lower the chances of early births by up to 34%. Although direct research on using vaginal progesterone for vaginal atrophy is lacking, progesterone's effect on vaginal tissues suggests potential benefits. Since it addresses other reproductive system issues, it might also alleviate symptoms of vaginal atrophy. This treatment is considered for those who cannot or prefer not to use estrogen therapies. ^{6 7 8 9 10}

Who Is on the Research Team?

Wendy L Wolfman, MD, FRCSC

Principal Investigator

MOUNT SINAI HOSPITAL

Are You a Good Fit for This Trial?

Inclusion Criteria

Age greater than or equal to 45, unless the patient has had a bilateral oophorectomy

Amenorrheic for greater than one year and/or FSH > 40IU/mL

Women who have had a bilateral oophorectomy will be eligible at any age

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either vaginal progesterone or placebo suppositories for 12 weeks

12 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Vaginal Progesterone

How Is the Trial Designed?

Group I: Vaginal Progesterone Experimental Treatment 1 Intervention

In the experimental arm, the participants will be randomized (1:1 allocation) to receive a vaginal progesterone suppository (100mg) as the intervention. Participants will be instructed to insert the vaginal suppository into the vagina, as high as is comfortable for the patient. They are to insert the drug three days per week, on Monday, Wednesday and Fridays, preferably at bedtime. Patients will record the use of their medications. This will be done for the study period of 12 weeks.

Group II: Placebo Comparator Placebo Group 1 Intervention

In the placebo arm, the participants will be randomized (1:1 allocation) to receive a vaginal suppository (100mg) containing hard fat without any active hormonal ingredient as the intervention. Participants will be instructed to insert the vaginal suppository into the vagina, as high as is comfortable for the patient. They are to insert the placebo three days per week, on Monday, Wednesday and Fridays, preferably at bedtime. Patients will record the use of their medications. This will be done for the study period of 12 weeks.

Who Is Running the Clinical Trial?

Mount Sinai Hospital, Canada

Lead Sponsor

Trials

210

Recruited

70,700+

Published Research Related to This Trial

In a study of 60 infertile patients, both Cyclogest vaginal suppositories and Crinone 8% vaginal gel were found to cause similar levels of perineal irritation, with about 20% of patients reporting this side effect.

However, significantly more patients using Cyclogest reported moderate to severe inconvenience related to administration, leaking, and interference with sexual activity, suggesting that Crinone gel may be a more user-friendly option for luteal support in IVF cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised comparison of side effects and patient inconvenience of two vaginal progesterone formulations used for luteal support in in vitro fertilisation cycles. Ng, EH., Miao, B., Cheung, W., et al.[2022]

In a meta-analysis of two phase III trials involving 1435 IVF patients, subcutaneous progesterone did not show any significant difference in ongoing pregnancy rates or live birth rates compared to vaginal progesterone.

Both methods of progesterone administration had similar safety profiles, with no significant differences in the risk of ovarian hyperstimulation syndrome (OHSS), indicating that subcutaneous progesterone is a viable alternative for luteal phase support in IVF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Progesterone Is Effective and Safe for Luteal Phase Support in IVF: An Individual Patient Data Meta-Analysis of the Phase III Trials. Doblinger, J., Cometti, B., Trevisan, S., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5987201/

VAGINAL PROGESTERONE FOR PREVENTING PRETERM ... That meta-analysis showed that vaginal progesterone significantly reduced the risk of preterm birth ≤34 weeks or fetal death by 34%. Subsequently, the lead ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10017734/

The effectiveness of vaginal progesterone in reducing ... Progesterone treatment was associated with a reduction in rates of spontaneous preterm birth before 34 weeks of gestation, neonatal intensive care unit ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1701216322002444

Retrospective Review of Reproductive Outcomes ... Our data demonstrated no difference between PIO and VP with respect to the rates of pregnancy (51% vs. 53%), miscarriage (20% vs. 18%), or live birth (31% vs.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2797994

Evaluating Vaginal Progesterone in Preventing Recurrent ... Nelson et al suggest that vaginal progesterone was not associated with a reduction in risk of recurrent preterm birth; a notable feature of the ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1813730

A Randomized Trial of Progesterone in Women with ... In conclusion, treatment with progesterone did not result in significant improvement in the incidence of live births among women with vaginal ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2008/022057s001lbl.pdf

Endometrin® (progesterone) Vaginal Insert - accessdata.fda.gov The safety data reflect exposure to Endometrin in 808 infertile women (74.9% White, 10.3% Hispanic, 5.4% Black, 5% Asian, and 4.6% Other) in a single ...

7. media.allergan.com media.allergan.com/actavis/actavis/media/allergan-pdf-documents/safety-data-sheets/PROGESTERONE-GEL-8percent-MIX-199791-AGHS-EN.pdf

SAFETY DATA SHEET This safety data sheet is written to provide health, safety and environmental information for people handling this formulated product.

8. osha.gov osha.gov/chemicaldata/881

PROGESTERONE | Occupational Safety and Health ... PROGESTERONE: Chemical Identification, Physical Properties, Monitoring Methods Used by OSHA. All sampling instructions above are recommended guidelines.

9. sigmaaldrich.com sigmaaldrich.com/IN/en/sds/sigma/p0130?srsltid=AfmBOorl3OGvYuV-zIGAdFMpxLcO3uWYFa_1ziTPsNZuhHbES8g7yrno

SAFETY DATA SHEET WARNING: This product can expose you to chemicals including Progesterone, which is/are known to the State of California to cause cancer. For ...

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32074281/

Efficacy, safety and tolerability of progesterone vaginal ... Progesterone 400 mg pessaries bid for luteal phase support is an effective, safe and tolerable treatment option for women undergoing IVF during ART.