This phase II trial tests the feasibility and side effects of vaginal DHEA to improve vaginal health after radiation for women with gynecologic, anal or rectal cancer. Treatment of cancers with radiation to the abdomen can influence the vaginal microbiome (any bacteria, virus, or other organisms found in the vagina). Both menopause and radiation cause a decrease in lubrication and elasticity of the vagina and symptoms including vaginal dryness, vaginal burning and itching, vaginal bleeding, pain or burning during urination, and pain during sexual intercourse. DHEA is a type of hormone replacement therapy. It is use to improve symptoms in women during menopause and may be effective in treating these symptoms for women who have received radiation.

PRIMARY OBJECTIVE:

I. To determine the feasibility and tolerability of dehydroepiandrosterone (DHEA) in the post radiation setting for women with gynecologic and gastrointestinal cancers.

SECONDARY OBJECTIVES:

I. To identify changes from baseline to post-radiation in the vaginal microbiome in women with gynecologic and gastrointestinal cancers receiving vaginal DHEA.

II. To identify those who may respond to vaginal DHEA based on their pretreatment microbiome.

III. To correlate changes in vaginal exam findings, sexual function, and quality of life with changes in the vaginal microbiome.

OUTLINE:

Patients receive DHEA vaginally once daily (OD) for 3 months in the absence of disease progression or unacceptable toxicity. Patients undergo vaginal swab sample collection throughout the study.

Inclusion Criteria:

• Any patient with anal, rectal, cervical, vaginal, or vulvar cancer receiving external beam radiation alone, or both external beam radiation and brachytherapy with curative intent (Participants will be consented and enrolled prior to starting treatment but will not receive intervention till after treatment is completed)
• Concurrent or prior chemotherapy is allowed
• Any prior gynecologic surgery is permitted
• Rectal surgery, including lower anterior resection and abdominoperineal resection, is permitted
• Subject must be menopausal, which is defined as age > 50 with no menses for 12 months or bilateral oophorectomy

Exclusion Criteria:

• Patients with scleroderma, mixed connective tissue disorder, and lupus will be excluded
• Patients who have received prior pelvic radiation
• Undiagnosed abnormal genital bleeding (unrelated to current diagnosis or treatment related toxicity)
• Endometrial cancer or endometrial hyperplasia
• Use of estrogen alone injectable or progestin implant therapy with 3 months before study entry
• Use of estrogen pellet or progestin injectable drug within 6 months before study entry
• Use of oral estrogen, progestin, or DHEA or intrauterine progestin within 8 weeks before study entry
• Use of vaginal estrogen (rings, creams, tablets, or gels), transdermal estrogen +/- progestin, vaginal hyaluronic acid, or pro-estrogenic herbal treatments such as black cohosh in the 4 weeks before study entry. Intravaginal moisturizers and lubricants prior to enrollment are permitted
• History of breast cancer
• Patients receiving palliative radiation therapy
• Patients who do not meet criteria for menopause