Genitourinary Syndrome of Menopause: New Name, Old Problem

Previously known as atrophic vaginitis, vulvovaginal atrophy (VVA), or urogenital atrophy, genitourinary syndrome of menopause (GSM) is a composite of genital, urologic and sexual sequelae of chronic hypoestrogenism.  Sexual dysfunction and quality of life impairment are important to identify, as treatment options are available. Incidence is unknown as the syndrome is often underreported by women due to embarrassment, disregard, or a sense of inevitability.

KEY POINTS:

Risk Factors

  • Lactation
  • Hyperprolactinemia
  • Autoimmune disorders
  • Bilateral oophorectomy
  • Pelvic radiation
  • Chemotherapy
  • Medications including
    • GnRH agonists (leuprolide, nafarelin)
    • SERMs (such as tamoxifen)
    • Aromatase inhibitors,
    • Danazol
    • Progestins
  • Lifestyle risk factors including
    • Cigarette smoking, Alcohol abuse | Sexual abstinence | Lack of exercise | Lack of vaginal birth

Diagnosis

  • Include the following on history
    • Irritants: Lubricants, powders, soaps, spermicides, panty liners
    • Hypoestrogenism: Oophorectomy, antiestrogen medications, radiation, chemotherapy
  • Ask about the following symptoms
    • Vulvovaginal: Itching, burning, pain, discharge, dyspareunia
    • Urinary: Frequency, dysuria, urgency, dribbling, incontinence, recurrent urinary tract infections
  • On pelvic exam look for the following
    • Pale vaginal epithelium with areas of erythema
    • Lacerations, stenosis, friable epithelium, labial fusion
  • Consider the following on differential diagnosis
    • Infection
    • Contact irritants
    • Foreign body
    • Sexual trauma
    • Neoplasm
    • Radiation effect
    • Dermatologic conditions such as lichen sclerosis or lichen planus
  • Diagnostic tests should be individualized and risk-based
    • Vaginal pH (5-7 in GSM)
    • Vaginal cytology (primarily basal cells)
    • Wet mount
    • Cervical cytology
    • Depending on history and physical findings, other tests to consider
      • Transvaginal ultrasound
      • Hysteroscopy

Treatment

Estrogen Therapy (Summary of dosage regimens can be found in the ObG NAMS entry below)

  • Management of moderate/severe GSM is best treated with estrogen therapy (ET)
    • Up to 90% of women will improve with local ET, whether vaginal ring, cream, gel, or tablet
      • Progestin is not necessary to protect the endometrium
      • Treatment is long term
  • Consider systemic ET in patients with GSM and/or vasomotor symptoms, risk factors for osteoporosis
    • Progestin needed in women with an intact uterus
    • Both systemic and local ET may be necessary based on clinical response

Estrogen Therapy Alternatives (More information including medications can be found in ObG entries below)

  • Be mindful of contraindications and precautions related to ET use (see “Special Populations” below)
    • Known/suspected breast cancer | Estrogen-dependent cancers | Undiagnosed vaginal bleeding | Endometrial hyperplasia/cancer | Hypertension | Hyperlipidemia | Liver disease | History of CVA/VTE/CAD or thrombophilic disorders (e.g., protein C, protein S, antithrombin deficiency) | Pregnancy | Smoking | Migraine with aura | Acute cholecystitis/cholangitis
  • Other options include the following
    • SERMs, such as ospemifene and bazedoxifene
      • Contraindications: Undiagnosed abnormal genital bleeding | Known or suspected estrogen-dependent neoplasia | Active arterial thromboembolic event
    • Vaginal dehydroepiandrosterone (DHEA) – Prasterone
      • Contraindications: Undiagnosed abnormal genital bleeding
    • Tibolone (Not available in US or Canada)
    • Moisturizers and lubricants
  • Homeopathic remedies have no proven efficacy on the vaginal epithelium and treatment of GSM
  • Smoking cessation may be helpful

Special Populations: History of Estrogen Dependent Breast Cancer

Nonhormonal Methods: First Line Therapy

  • Lubricants: Silicone | Polycarbophil | Water based
  • Moisturizers: Hyaluronic acid | Polyacrylic acid | Polycarbophil based
  • Vaginal suppositories: Vitamin E | Vitamin D
  • 4% aqueous lidocaine: Applied to vulvar vestibule
  • Laser therapy: Not currently FDA approved | Additional research needed before recommending

Hormonal Methods: Consider if Nonhormonal Treatments Fail 

  • Low dose vaginal estrogen 
    • Discuss risks/benefits 
    • Can be used with history of breast cancer 
    • Can be used if taking tamoxifen 

Note: If patient taking aromatase inhibitor, decision should involve oncologist 

  • Vaginal Dihydroepiandrosterone (DHEA) or testosterone 
    • Can help with dyspareunia and vaginal atrophy 
    • Second line to vaginal estrogen 
  • Ospemifene/SERMs 
    • Long term safety data in patients with ER-dependent breast cancer is limited 
    • Can be considered 

Learn More – Primary Sources:

ACOG Practice Bulletin 141: Management of Menopausal Symptoms

Perspective on prescribing conjugated estrogens/bazedoxifene for estrogen-deficiency symptoms of menopause: a practical guide

Kaunitz and Manson: Management of Menopausal Symptoms

ACOG Clinical Consensus 2: Treatment of Urogenital Symptoms in Individuals With a History of Estrogen-dependent Breast Cancer

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

Effect of a pH-balanced vaginal gel on dyspareunia and sexual function in breast cancer survivors who were premenopausal at diagnosis: a randomized controlled trial

JAMA Insights: Treatment of Vulvovaginal Atrophy

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

Treating Postmenopausal Vaginal Atrophy When Estrogen is Not an Option

CLINICAL ACTIONS:

If a patient complains of dyspareunia, and clinical examination is consistent with postmenopausal vaginal atrophy / atrophic vaginitis, local estrogen is the first line of treatment, but there are alternatives that can be considered if the following two criteria are met:

  • Ascertain if the patient can, indeed, use estrogen and ensure that option was offered and an informed decision to decline was met
  • Screen for a history of breast or uterine cancer, history of blood clots or liver conditions

SYNOPSIS:

Some postmenopausal patients will not or cannot use local estrogen replacement therapy to treat vaginal atrophy/atrophic vaginitis. Common situations in which this is the case may include personal history of estrogen-sensitive breast cancer or endometrial cancer, although NAMS guidelines do recommend that low-dose local HT may be an option, in consultation with a patient’s oncologist in certain situations. Fortunately, a number of effective options are available for these women.

When a clinician cannot prescribe local estrogen, alternatives for postmenopausal vaginal atrophy include

  •  Ospemifene – 60 mg daily
    • Should not be used concomitantly with estrogens
    • Should be used for 12 continuous weeks in order to gauge effectiveness
    • Ospemifene is a SERM
      • According to the FDA, there is insufficient data to use ospemifene in women with breast cancer
      • While there do not appear to be any cases of ospemifene causing endometrial cancer, a potential risk for this particular malignancy is mentioned in a boxed warning
  • Prasterone – One vaginal insert (6.5 mg) each evening at bedtime
    • FDA approved, steroid-based treatment for postmenopausal vaginal atrophy
    • Use is appropriate for women who complain of dyspareunia due to dryness and thinning of the vaginal mucosa
    • 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
  • Lubricants
    • Have been found to be efficacious and may help alleviate symptoms

Laser Treatment – FDA Statement

  • The FDA has released a statement (August 2018) warning that “…safety and effectiveness of these devices hasn’t been evaluated or confirmed by the FDA for “vaginal rejuvenation.” In addition to the deceptive health claims being made with respect to these uses, the “vaginal rejuvenation” procedures have serious risks.”
  • ACOG supports the FDA statement and has a position statement advising that while there is there is FDA clearance of fractional C02 laser, indications do not specify treatment of vulvovaginal atrophy, but do include

incision, excision, ablation, vaporization, and coagulation of body soft tissues in medical specialties, including aesthetic (dermatology and plastic surgery), podiatry, otolaryngology (ENT), gynaecology, neurosurgery, orthopaedics, general and thorasic surgery (including open and endoscopic), dental and oral surgery and genitourinary surgery

  • NAMS has also responded and while welcoming the FDA’s mandate requiring companies to provide adequate data, the NAMS statement includes the following to assist with counseling

NAMS recommends that healthcare providers discuss the benefits and risks of all available treatment options for vaginal symptoms, including over-the-counter lubricants, vaginal moisturizers, and FDA-approved vaginal therapies such as vaginal estrogen and
intravaginal dehydroepiandrosterone and oral therapies such as hormone therapy and ospemifene to determine the best treatment for women with GSM. When discussing vaginal energy-based therapies, informed discussion should include that these are FDA-approved devices for gynecology but have not received FDA approval for vaginal rejuvenation or procedures for GSM, sexual function, incontinence, or pelvic laxity and that even though short-term data are promising, more robust, sham-controlled, and longer-term data are needed.

KEY POINTS:

  • While alternative treatments will address vaginal dryness and atrophy, patients should be informed of the limitations of these treatments
  • Treatments that are effective for managing vaginal atrophy, may not help with other menopausal symptoms such as hot flashes, night sweats or mood

Learn More – Primary Sources:

Effect of Ospemifene on Moderate or Severe Symptoms of Vulvar and Vaginal Atrophy

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

ACOG Position Statement: Fractional Laser Treatment of Vulvovaginal Atrophy and U.S. Food and Drug Administration Clearance

FDA Statement: Statement from FDA Commissioner Scott Gottlieb, M.D., on efforts to safeguard women’s health from deceptive health claims and significant risks related to devices marketed for use in medical procedures for “vaginal rejuvenation”

NAMS Response: FDA Mandating Vaginal Laser Manufacturers Present Valid Data Before Marketing