Prasterone for Vulvovaginal Atrophy – What is it and How to Prescribe

CLINICAL ACTIONS:

Vulvovaginal atrophy is a common symptom of atrophic vaginitis (also referred to as the genitourinary syndrome of menopause or GSM) and can occur in both perimenopausal and postmenopausal women. If a patient reports vaginal dryness consider the following:

• Confirm diagnosis of postmenopausal atrophy through vaginal exam
• Discuss use of vaginal estrogen as an option
• If patient is not an appropriate candidate for local estrogen or if patient would prefer not to use a direct estrogen product, prasterone may be an effective alternative
  • One vaginal insert (6.5 mg of prasterone) each evening at bedtime

SYNOPSIS:

Prasterone is an approved, steroid-based FDA treatment for postmenopausal vaginal atrophy. Use is appropriate for women who complain of dyspareunia, or general discomfort due to dryness and thinning of the vaginal mucosa.

KEY POINTS:

• During perimenopause and menopause, estrogen levels decline in vaginal tissues and is referred to as vulvovaginal atrophy (VVA), which may result in discomfort or pain during intercourse
  • Local estrogen can be considered a first line treatment of VVA but may not be appropriate or desired by all patients
• The FDA approved prasterone to treat women experiencing moderate to severe dyspareunia, a symptom of VVA, due to menopause
  • Prasterone is the first FDA approved product containing the synthetic active ingredient dehydroepiandrosterone (DHEA)
• DHEA can convert to androgens and/or estrogens and, while the likelihood is low and the quantities minimal, a physician should disclose the following
  • Based on the fact that there is minimal data on safety in the setting of hormonally sensitive malignancy, the FDA warns against using prasterone if there is a history of or known or suspected breast cancer
  • Unexplained uterine bleeding is a contraindication to use
  • It is indicated for use only in postmenopausal women

Learn More – Primary Sources:

FDA approves Intrarosa for postmenopausal women experiencing pain during sex

FDA: Prescribing information for Intrarosa (prasterone)

ACOG Committee Opinion No. 659: The Use of Vaginal Estrogen in Women With a History of Estrogen Dependent Breast Cancer

Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management

Diagnosing Vaginitis – Why the Office Visit Still Matters

CLINICAL ACTIONS:

A patient presents with vaginal inflammation with discharge, pain and/or itching. Next steps should include

Problem-focused history

• BV
  • Fishy odor | Thin homogeneous discharge (possibly worse after intercourse)
• Candidiasis
  • No odor | White, thick, ‘curdlike’ or ‘cheesy’ discharge | Itching and/or burning
• Trichomoniasis
  • Foul odor | Green or yellow, frothy discharge | Vaginal pain or soreness
• Atrophic vaginitis
  • Thin, clear discharge | Dryness | Dyspareunia | Itching
• Irritant/allergic vaginitis
  • Burning and/or soreness
• Desquamative Inflammatory vaginitis
  • Green or yellow (purulent) discharge | Burning | Dyspareunia

Exam including inspection of the vulva, vagina and cervix

• BV
  • Inflammation not usually present
• Candidiasis
  • Erythema | Edema
• Trichomoniasis
  • Inflammation | Strawberry Cervix
• Atrophic vaginitis
  • Inflammation | Thin/friable mucosa
• Irritant/allergic vaginitis
  • Erythema
• Desquamative Inflammatory vaginitis (DIV)
  • Varying vestibular and vaginal erythema

Appropriate laboratory testing

• Collection of and microscopic examination of a 10% KOH and saline prep (wet mount), pH testing and ‘whiff test’ constitute the office-based clinical testing of samples
• Culture (if necessary)
  • Yeast: Obtain if recurrent candidiasis or possible non-albicans Candida (suspect if blastospores ‘only’ or persistent treatment after treatment) | Negative microscopy with signs and/or symptoms of candidiasis
  • Trichomoniasis: ACOG recommends culture with a negative wet mount in the following circumstances
    • Persistent symptoms following treatment | high vaginal pH and WBCs on microscopy | Pap suspicious for T. vaginalis | patient desire for screening
    •  Note: CDC considers NAAT screening more sensitive for T. vaginalis then culture (previous gold standard) or wet mount
  • Mucopurulent cervicitis: Test (DNA or cultures) for gonorrhea or chlamydia
  • HSV: If any vulvar fissure/lesion suggestive of herpes simplex virus, perform viral culture or PCR assay for HSV DNA by swabbing the lesion
    • Type-specific HSV serologic assays might be useful in the following scenarios: 1) recurrent genital symptoms or atypical symptoms with negative HSV PCR or culture; 2) clinical diagnosis of genital herpes without laboratory confirmation (CDC STD Guidelines)

Perform “Whiff Test” with 10% KOH and Microscopy with Saline

• Positive whiff test
  • Negative (-) for WBC: Treat for bacterial vaginosis (BV)
  • Positive (+) for WBC: Review signs/symptoms for trichomoniasis or mixed bacterial vaginosis or cervicitis
• Negative whiff test
  • negative (-) for WBC: Noninfectious

Determine Vaginal pH

• If pH is normal (<4.7) consider the following
  • Infectious: Vulvovaginal candidiasis | Genital herpes
  • Noninfectious: Physiologic leukorrhea | Vulvodynia | Dermatitis/dermatoses

If pH is Elevated (>4.7) Consider the Following

• Infectious
  • Bacterial vaginosis | Trichomoniasis | Cervicitis
• Noninfectious
  • Blood | Semen | Atrophic vaginitis | Lichen planus | Desquamative inflammatory vaginitis (DIV)

SYNOPSIS:

Vaginitis is a general term for disorders of the vagina, but does not indicate the underlying cause.  Vaginitis may result from infection, inflammation, or may reflect changes in the normal vaginal microbiome.  The disorder is termed vulvovaginosis when the vulva is involved. When patients present with symptoms of itching/burning/irritation/dyspareunia/discharge consider a broad range of possibilities including but not limited to the triad of bacterial vaginosis (BV), trichomoniasis and vulvovaginal candidiasis.  Office based tests such as those above also have a low sensitivity. Accurate diagnosis may require a combination of a careful history, vulvar or vaginal biopsy and appropriate culture.

KEY POINTS:

• Self-diagnosis and treatment, while convenient, may be unreliable and results in frequent misuse of OTC products
• FDA approved commercial tests for BV
  • ACOG acknowledges that direct DNA probe assays for G vaginalis or chromogenic point-of-care assays for sialidase activity have acceptable performance vs Amsel criteria and Nugent scoring
  • However, because these tests only pick up one organism (i.e., G vaginalis) “the diagnostic utility of a test that identifies only a single organism (eg G vaginalis) is still being investigated and is not currently supported”
• No microscope
  • Vaginal pH testing narrows the differential diagnosis of vaginitis for BV and trichomoniasis
  • Candidiasis: History | Exam | Culture
  • Obtain vaginal secretions slide for future Gram stain if possible
• Incidental findings on Pap test
  • Not diagnostic
  • BV on Pap
    • Symptomatic: pH, amine test, and wet mount
    • Asymptomatic: Do not treat
  • Trichomoniasis on Pap
    • High false-positive rate (8% standard and 4% liquid-based)
    • Wet mount for confirmation
    • If wet mount negative, NAAT or culture
    • If diagnostic tests not available, can consider metronidazole, but high rate of unnecessary treatment

Learn More – Primary Sources:

ACOG Practice Bulletin 215: Vaginitis in Nonpregnant Patients 

Vaginitis: Diagnosis and Treatment

Advances in Diagnosing Vaginitis: Development of a New Algorithm