Local Estrogen Treatment Options for Vaginal Atrophy

CLINICAL ACTIONS:

A growing number of estrogen treatment options are available for postmenopausal vaginal atrophy. 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

  • Establish a diagnosis of postmenopausal atrophy based on thorough history and physical exam
    • Confirm with an appropriate pelvic/ vaginal exam
  • Discuss use of estrogen, understanding that for some women based on medical history, systemic estrogen might not be an appropriate option
    • Even with a personal history of cancer, local estrogen may be an appropriate treatment (see ‘Key Points’ and ‘Related ObG Topics’ below) depending on the clinical scenario
  • Vaginal estrogens can be prescribed as
    • A cream inserted twice weekly using an applicator
    • A tablet inserted with an applicator
    • A soft gel pellet inserted twice weekly with no applicator (FDA approved May, 2018)
    • Ring made of silicone elastomere containing a drug core of estradiol hemihydrate (replaced every 3 months)

Local Estrogen Routes and Dosing for GSM

  • Estradiol-17β ring (releases 7.5 micrograms/d)
    • Replace every 3 months
  • Estradiol vaginal tablet (10 micrograms/d)
    • Place nightly for 2 weeks
    • Maintenance is one tablet 2 times/week
    • Note: this is the corrected dose in ACOG PB 141
  • Estradiol-17β cream (0.1 mg active ingredient/g)
    • 2-4 g/d for 1 to 2 weeks
    • Gradually reduce to ½ initial dosage for 1 – 2 weeks
    • Maintenance is 1 g, 1 to 3 times/week
  • Conjugated estrogen cream (0.625 mg/g)
    • 0.5–2 g/d for 21 days then off for 7 days
    • In practice during maintenance therapy, most women apply 1 – 3 times /week
  • Vaginal inserts (4-μg and 10-μg)
    • 1 vaginal insert daily for 2 weeks
    • Maintenance is 1 insert twice weekly

SYNOPSIS:

Patients may experience vaginal atrophy as itching, dryness or pain during sexual activity. Vaginal estrogen has been shown to improve moderate to severe menopausal vaginal atrophy. Options for topical estrogen treatment are increasing. Women’s healthcare professionals need to confirm appropriate use of estrogen and help patients identify which treatment option will work best for their situation and lifestyle.

KEY POINTS:

  • During perimenopause and menopause, estrogen levels decline in vaginal tissues
    • Referred to as vulvovaginal atrophy (VVA), this may result in discomfort or pain during intercourse or general dryness and discomfort
  • If patient complains of dyspareunia, and clinical examination is consistent with postmenopausal vaginal atrophy / atrophic vaginitis, local estrogen is the first line and most effective treatment
    • Estrogen treatment may not be appropriate or desired by all patients
  • Ascertain if estrogen is an appropriate option for the patient
    • Screen for a history of breast or uterine cancer
    • History of blood clots
    • Liver conditions
  • If patient is appropriate for treatment with local estrogen, offering the spectrum of choices can help a patient identify the product that will work best for them
  • While there is a theoretical concern regarding systemic estrogen absorption and risk for uterine cancer, based on evidence, professional organizations  consider “the addition of progestin for endometrial protection is not needed” (ACOG)

Differentiating factors include

  • Creams
    • Can be used on the vulva as well as internally in the vagina
  • Tablets or caplets
    • Some can be used during the day
    • Some tablets may need to be used at night because of the way they dissolve
  • Applicators
    • May be an issue of patient preference and warrants discussion
  • Ring
    • Benefits include ease of use
    • For some women, there may be structural issues related to comfort and/or retention  (e.g., short or narrow vagina / prolapse)
  • Make patients aware that there are non-estrogen options available for use by women who are not appropriate candidates for local estrogen including
    • Prasterone | Ospemifene
  • Laser Treatments have been advocated as a possible treatment, however VVA not a currently FDA-approved indication

Learn More – Primary Sources:

The 2017 hormone therapy position statement of The North American Menopause Society

Scientific Background Report for the 2017 Hormone Therapy Position Statement of The North American Menopause Society

ACOG Practice Bulletin 141: Management of Menopausal Symptoms

Practice Bulletin 141: Management of Menopausal Symptoms: Correction

A Randomized, Multicenter, Double-Blind, Study to Evaluate the Safety and Efficacy of Estradiol Vaginal Cream 0.003% in Postmenopausal Women with Vaginal Dryness as the Most Bothersome Symptom.

FDA Highlights of Prescribing Information for IMVEXXY

Drugs@FDA: Estring

Drugs@FDA: Estrace Cream

Drugs@FDA: Premarin Vaginal Cream 

Drugs@FDA: Vagifem Tablet 

Estradiol vaginal inserts (4 µg and 10 µg) for treating moderate to severe vulvar and vaginal atrophy: a review of phase 3 safety, efficacy and pharmacokinetic data

Reviewing the options for local estrogen treatment of vaginal atrophy

Screening for Sexual Assault

CLINICAL ACTIONS:

ACOG recommends that health care providers screen all women for a history of sexual assault. Screening should take place during routine wellness exams or when presented with symptoms that are suspicious for sexual assault (see ‘Red Flags’ below, in KEY POINTS).  

The National Sexual Violence Resource Center recommends the following to further engage women in a discussion regarding sexual assault  

    • Normalize the subject by including it within the sexual history; ACOG recommends the following introduction  
      • “Because sexual violence is an enormous problem for women in this country and can affect a woman’s health and well-being, I now ask all my patients about exposure to violence and about sexual assault.” 
    • Provide context by connecting the subject to the patient’s health and well-being 
    • Be nonjudgmental 
    • Validate the patient’s responses
  • Ask about sexual experiences that were uncomfortable or unwanted 
      • Have you been touched without your consent? 
      • Have you ever been pressured or forced to have sexual contact? 
    • Do you feel that you have control over your sexual relationships? 

SYNOPSIS:

Key findings of the National Intimate Partner and Sexual Violence Survey reveal that an estimated 1.3 million rape-related physical assaults occur against women annually. Early identification of victims can lead to prevention of long-term and persistent physical and mental health consequences of abuse.  

KEY POINTS:

  • Decide on appropriate interventions depending on each individual situation
  • Pay particular attention to those who report pelvic pain, dysmenorrhea, or sexual dysfunction
  • Red Flags’ for sexual assault include
    • Anxiety
    • Depression
    • Sudden-onset sleep disorders
    • Stress-related complaints
    • Requests for
      • Pregnancy testing
      • Emergency contraception
      • Testing for sexually transmitted diseases
      • Pelvic area trauma
      • Bruising that may be from restraints

Learn More – Primary Sources:

ACOG: Screening Tools – Sexual Assault

ACOG Committee Opinion 777: Sexual Assault

ACOG Committee Opinion 518: Intimate Partner Violence

National Sexual Violence Resource Center

Assessing Patients for Sexual Violence: A guide for health care providers (NSVRC) 

Screening & Treatment of Gynecologic infections in the HIV-Positive Woman

Gynecologic infections are more common, and may be more difficult to eradicate, in the HIV population.  Overall, treatment protocols remain the same, irrespective of HIV status, although there are some differences depending on the disorder.

CLINICAL ACTIONS:

  • Screen at entry to care and at least annually for the following: N. gonorrhoeae, C. trachomatis, syphilis and vaginal trichomoniasis
  • Screen for hepatitis C on entry to care
    • At-risk seronegative individuals should be screened at least annually
  • Consider type specific HSV serologic testing for those presenting for an STD evaluation
    • Approximately 70% of persons with HIV are HSV-2 seropositive | 95% are seropositive for either HSV-1 or HSV-2
    • HSV-2 infection increases the risk of HIV acquisition two- to three-fold and in coinfected patients
    • HSV-2 reactivation results in increases in HIV RNA levels in blood and genital secretions
  • Screen on entry to care for hepatitis B with HBsAg, anti-HBc and/or anti-HBs
    • Offer vaccination to seronegative individuals with hepatitis B or combined hepatitis A and B vaccine
    • Recheck immunity after vaccination complete

SYNOPSIS:

While it is critical to remain vigilant with regard to STDs and pelvic infections, women with ulcerative conditions of the genitalia, including syphilis and herpes, are at increased risk of HIV acquisition and transmission to partners, lending an urgency to prompt treatment or suppression (see separate entry on ulcerative conditions).

KEY POINTS:

  • Bacterial vaginosis is more prevalent/persistent in HIV-positive women
    • Diagnosis and treatment options are the same
  • Vulvovaginal candidiasis is more common among HIV-positive women and associated with decreased CD4+ counts
    • Treatment is the same as for HIV-negative women
    • For azole-refractory Candida glabrata vaginitis
      • Boric acid 600 mg vaginal suppository once daily for 14 days
    • Note: Severe or recurrent vaginitis should be treated with oral fluconazole (100 to 200 mg) or topical antifungals for ≥7 days
  • Treatment for gonorrhea/chlamydia is the same as for HIV-negative women
    • Retest 3 months after treatment as reinfection is common
  • Pelvic inflammatory disease is treated with the same antimicrobials for the same duration as for HIV-negative
    • There is a greater incidence of tubo-ovarian abscess among HIV-positive, but overall response to therapy is the same as for HIV-negative
  • Trichomoniasis is more prevalent among HIV-positive and should be treated with a one week course of metronidazole
  • Parasitic conditions such as scabies or pediculosis pubis are treated the same regardless of HIV status

Learn More – Primary Sources:

ACOG Practice Bulletin 167: Gynecologic Care for Women and Adolescents with Human Immunodeficiency Virus

NIH Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents

CDC: Sexually Transmitted Infections Treatment Guidelines 2021

Talking to Your Patients About OTC DHEA

CLINICAL ACTIONS:

Patient complaints regarding sexual functioning, either lowered levels of desire, or difficulty becoming aroused, are common. Currently, there are drugs, such as testosterone, that are being used ‘off label’ for this purpose. A patient may request a trial of a ‘more natural’ alternative, available over the counter (OTC) such as Dehydroepiandrosterone (DHEA). In this setting, consider discussing the following

  • Because DHEA converts into testosterone, ongoing use of DHEA may result in side effects associated with testosterone use
  • Side effects of DHEA are generally less severe than testosterone, although patients may experience some hair growth, oily skin or acne
  • In very high doses, more than 1600 milligrams daily, DHEA can have the same significant side effects as testosterone: hair growth, hair loss on the head, voice deepening and clitoral enlargement

SYNOPSIS:

Data support the positive role of androgens in female sexual function and ovarian physiology. However, the availability of approved testosterone formulations remains limited, particularly in the US. Therefore, patients may opt to obtain DHEA, the precursor hormone, in its stead.  There is no positive guidance regarding the use of DHEA in women for sexual dysfunction because currently there remains a lack of well-designed studies demonstrating consistent clinical improvement.

KEY POINTS:

  • DHEA will convert into estrogen as well as testosterone and therefore extra caution to avoid this hormone may be reasonable in women with a history of breast or uterine cancer
  • DHEA is not FDA approved as a drug and therefore what is packaged may not be reliably indicated on the bottle
  • In a small but well-designed pilot study that studied sleep patterns in healthy postmenopausal women, DHEA supplementation can cause sleep stimulation or inhibition
  • ACOG states

Systemic DHEA has been tested but has not shown efficacy in postmenopausal women for treatment of sexual interest and arousal disorders and, therefore, is not recommended for use

Learn More – Primary Sources:

Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction

ACOG Practice Bulletin 213: Female Sexual Dysfunction

DHEA therapy for women: effect on sexual function and wellbeing

Effects of a 3-week dehydroepiandrosterone administration on sleep, sex steroids and multiple 24-h hormonal profiles in postmenopausal women: a pilot study

Sex Education and the ObGyn: the ACOG Committee Opinion

CLINICAL ACTIONS

Comprehensive sexuality education should be medically accurate, evidence-based, and age-appropriate. Obstetrician-gynecologists can take part in this by addressing issues directly with adolescent patients in the following ways:

  • Participate locally in development of community programs on sexuality utilizing evidence-based curricula that focus on clear health goals (e.g. the prevention of pregnancy and STDs, including HIV)
  • Provide health care that focuses on optimizing sexual and reproductive health and development
  • Aid in designing programs that cover the variations in sexual expression, including vaginal intercourse, oral sex, anal sex, mutual masturbation, as well as texting and virtual sex

SYNOPSIS:

Community and school-based programs are an important facet of sexuality education. However, a preponderance of evidence suggests that when a responsible adult talks about sexual topics with adolescents, there is delayed sexual initiation and increased birth control and condom use. Although many parents talk with their adolescents about risks and responsibilities of sexual activity, one-third to one-half of females aged 15–19 years report never having talked with a parent about contraception, STDs, or “how to say no to sex.” The gynecologist can also play an important supporting role in this dialogue by open discussions with parents, guardians and adolescents.

KEY POINTS:

  • Sexuality education should be evidence-based and should include the benefits of delaying sexual intercourse, while also providing information about normal reproductive development, contraception (including long-acting reversible contraception methods) to prevent unintended pregnancies, as well as barrier protection to prevent STDs
  • Sex education should be tailored to specific ethnicities and cultural groups and should be inclusive of those with physical, and cognitive disabilities
  • Sex education should not marginalize lesbian, gay, bisexual, questioning, and transgender individuals and those that have variations in sexual development
  • Studies have demonstrated that comprehensive sexuality education programs reduce the rates of sexual activity, sexual risk behaviors (e.g. number of partners and unprotected intercourse, STDs, and adolescent pregnancy)
  • Obstetrician–gynecologists have the unique opportunity to act “bi-generationally” by asking their patients about their adolescents’ reproductive development and sexual education, human papillomavirus vaccination status, and contraceptive needs

Learn More – Primary Sources:

ACOG Committee Opinion 678: Comprehensive Sexuality Education

What and When to Tell Patients About Lubricants?

CLINICAL ACTIONS:

  • Inquire about patient’s use of lubricants if/when the patient expresses any discomfort with intercourse
  • Address misconceptions by educating women about lubricant basics and encourage women to try various lubricants until they find the one that works best for them
  • If a patient is currently using a lubricant during intercourse, it is likely that any experienced pain is due to causes other than vaginal dryness

SYNOPSIS:

Use of lubricants can be essential for allowing sexual intercourse to be pleasurable. Given the array of available options on the market, as well as numerous misconceptions regarding lubricants, women often find it helpful when providers educate them about available options and make recommendations. It is important to reassure women, especially young women, that the use of lubricants should not be considered shameful in any way, and that the need for lubricants is dependent on many physiological factors that are not age related.

KEY POINTS:

  • There are significant differences between lubricants, and there is no “one-size-fits-all” product
  • The “classic” lubricants, those which are most ubiquitous and often most popular due to effective advertising, are not necessarily the most effective
  • Lubricants are either water-based or silicone-based and differ significantly from each other
    • Silicone based lubricants last longer, feel silkier and can be used in water, but should not be used with silicone toys
    • Water based lubricants are experienced as “slicker and thinner”, dry up faster and are easier to clean
  • Textures vary from watery to more viscous, or “tacky”
  • Most women prefer those that remain more fluid for a longer time; however, each woman should try various options to determine what feels best for her and her partner
  • Pure coconut oil is a popular, effective and natural lubricant that is easily available
  • If patients are prone to yeast infections, they should avoid glycerin-based lubricants; this includes all flavored lubricants
  • Petroleum jelly (vaseline) should never be used as a lubricant
  • Lubricants should be used on partner’s penis, as well as on the vulva or intravaginally

Learn More – Primary Sources:

Treating vulvovaginal atrophy/genitourinary syndrome of menopause: how important is vaginal lubricant and moisturizer composition?

To Lube or Not to Lube: Experiences and Perceptions of Lubricant Use in Women With and Without Dyspareunia

A Randomized, Double-blind, Crossover Trial Comparing a Silicone-vs. Water-based Lubricant for Sexual Discomfort after Breast Cancer

Locate a Sexual Health Professional:

AASECT-Referral Directory 

ISSWSH-Find a Provider 

SSTAR-Find a Therapist