Vaginal Progesterone Versus Placebo for the Treatment of 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

Trial Summary

What is the purpose of this trial?

This trial is testing vaginal progesterone suppositories to treat post-menopausal women with vaginal dryness and inflammation who cannot use or do not respond to estrogen treatments. Progesterone may help by reducing inflammation and improving the health of the vaginal lining. Recent studies suggest that vaginally administered progesterone is selectively distributed to the uterus, potentially offering benefits in hormone replacement therapy. The goal is to find an effective alternative treatment for these women.

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.

What data supports the effectiveness of the drug Vaginal Progesterone?

Research shows that using vaginal progesterone can significantly reduce the risk of spontaneous abortions (miscarriages) in women who have had previous miscarriages. In one study, only 9% of pregnancies treated with vaginal progesterone resulted in miscarriage, compared to 42% in untreated pregnancies. ^{1 2 3 4 5}

Is progesterone safe for human use?

Progesterone, especially in its micronized natural form, is generally considered safe for human use with fewer side effects compared to synthetic versions. Common side effects of synthetic progestins can include fatigue, fluid retention, and changes in mood, while natural progesterone tends to have milder effects. ^{2 6 7 8 9}

How does the drug vaginal progesterone differ from other treatments for its condition?

Vaginal progesterone is unique because it is administered directly to the vagina, allowing for a direct transport to the uterus, which results in a preferential uptake of the hormone. This method provides effective support for the uterine lining with fewer systemic side effects compared to oral or synthetic progestins, making it particularly useful in conditions like infertility and hormone replacement therapy. ^{10 11 12 13 14}

Research Team

Wendy L Wolfman, MD, FRCSC

Principal Investigator

MOUNT SINAI HOSPITAL

Eligibility Criteria

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

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

Treatment Details

Interventions

• Placebo
• Vaginal Progesterone

Participant Groups

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+

Findings from Research

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]

References

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

Progesterone therapy to decrease first-trimester spontaneous abortions in previous aborters. [2013]

2. Pakistan pubmed.ncbi.nlm.nih.gov

Oral versus Vaginal Micronized Progesterone for the Treatment of Threatened Miscarriage. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

Vaginal progesterone after tubal pregnancy. [2019]

4. Ireland 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. [2022]

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

The efficacy of progesterone in achieving successful pregnancy: I. Prophylactic use during luteal phase in anovulatory women. [2013]

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

Progesterone: review of safety for clinical studies. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Progesterone and related progestins: potential new health benefits. [2022]

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

Using progestins in clinical practice. [2007]

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

Alternate delivery systems for contraceptive progestogens. [2013]

10. United States 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. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Progesterone in normal and pathological pregnancy. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Effect of randomized serum progesterone concentration on secretory endometrial histologic development and gene expression. [2023]

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

Uses of progesterone in clinical practice. [2013]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Progesterone supplementation to prevent recurrent miscarriage and to reduce implantation failure in assisted reproduction cycles. [2022]