Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen

This is a double-blind randomized trial of intravaginal estrogen (conjugated estrogens,
0.625mg/1g cream) vs. placebo in postmenopausal women (n=222 total) with symptomatic prolapse
beyond the hymen planning transvaginal native tissue repairs. Medication will be started 6-8
weeks before surgery and continued for 1 year postoperatively, i.e. until scar remodeling is
complete. The investigators aim to determine if pre- and postoperative intravaginal estrogen
therapy (i) results in anatomic and patient-reported subjective improvement in pelvic organ
support, and (ii) impacts other pelvic floor disorders (overactive bladder and incontinence,
sexual function and pain, postoperative cystitis), satisfaction, quality of life, and vaginal
wound healing. Finally, (iii) the investigators will determine the potential mechanisms by
which local estrogen treatment alters pelvic organ support by examining full-thickness
vaginal wall biopsies taken at the time of surgery for histologic, connective tissue, and
smooth muscle synthesis and degradative changes. The investigators expect this will highlight
other novel targets for future therapies in prolapse repair and prevention.

Inclusion Criteria:

- Postmenopausal: no menses for >1 year

- Minimum age: 48 years

- Symptomatic apical and/or anterior vaginal wall prolapse, stage 2 or greater

- No estrogen replacement within the last month (may come off current treatment, i.e.
wash out, to join the study)

- Medically fit for elective surgery

- Physically able to apply/insert the study drug

- Available for clinic follow-up for minimum 1yr

Exclusion Criteria:

- Concurrent use of steroid creams for other indications (e.g. lichen sclerosis)

- BMI >35 kg/m2

- Recent history (within last month) of vaginal infection or vaginitis

- Contraindications to estrogen therapy (e.g. spontaneous DVT, stroke, breast or
endometrial/ hormone-responsive cancer, genital bleeding of unknown cause)

- History of connective tissue disease

- Any oral or transdermal estrogen, SERM, or other medication impacting vaginal milieu

- History of vaginal irradiation

- Allergy to Premarin or its constituents

- Prior apical repair or use of mesh for prolapse repair

- Current tobacco use