Therapeutic options
for the treatment
of vaginal atrophy

Clinical Professor, Department of Obstetrics and Gynecology and Reproductive Sciences, University of California, San Francisco, East Bay Physicians Medial Group, Affiliated with Sutter East Bay Medical Foundation, Berkeley, Calif

DISCLOSURE
The author is a consultant/advisory board member for Amgen, Depomed, Eli Lilly, Novo Nordisk, Pfizer, Merck, Foundation for Osteoporosis Research and Education/American Bone Health; receives grants/research support from Boehringer Ingelheim, Depomed, Eli Lilly; and is a speaker for Amgen, Eli Lilly, Novartis, and Novo Nordisk.

Vaginal atrophy is a common condition that affects 7% to 57% of postmenopausal women and may lead to symptoms of burning, itching, dryness, irritation, and dyspareunia.^1-7 In contrast to vasomotor symptoms associated with menopause, symptoms of vaginal atrophy typically do not resolve without effective treatment and do not diminish over time.^1,8,9

Several effective therapeutic options exist for women who are living with vaginal atrophy, and these may be administered across the range of severity for temporary or chronic symptoms.¹⁰ Effective treatments range from nonhormonal over-the-counter creams and gels for mild symptoms, vaginal hormone therapy for persistent symptoms, and systemic estrogen therapy for treatment of the spectrum of postmenopausal symptoms.^11-14 This article reviews the therapeutic options available for treatment of vaginal atrophy, as well as the advantages and disadvantages of each option and strategies for optimizing treatment.

NONHORMONAL THERAPIES

For many women, nonhormonal options for therapy, such as over-the-counter lubricants or moisturizing products, are effective in relieving symptoms of vaginal atrophy.⁸ Vaginal moisturizers, such as Replens or K-Y products, have been shown to lower vaginal pH, promote elimination of dead cells, bind vaginal tissue, and increase vaginal moisture and fluid.^8,14-16 Moisturizers are generally used independently of sexual activity. Clinical data indicate that Replens is effective in improving symptoms of vaginal itching, irritation, and dyspareunia.¹⁴ Water-soluble lubricants are usually used to alleviate dryness during sexual activity. Although vaginal lubricants have been shown to decrease vaginal irritation during sexual activity, limited evidence about their long-term therapeutic effect is available.⁹

Findings also indicate that other lifestyle changes, including increase in coital activity, smoking cessation, and consumption of cranberry juice (for recurrent urinary tract infections) can also relieve symptoms of vaginal atrophy.⁸

VAGINAL ESTROGEN

Local estrogen therapy is the treatment of choice for women with vaginal atrophy who do not have any other postmenopausal symptoms, according to the 2010 North American Menopause Society (NAMS) guidelines.^11,17 The beneficial effects of estrogen therapy include both the improvement of symptoms associated with vaginal atrophy and the restoration of the vaginal anatomy.¹ Local estrogen therapy was associated with significant symptom improvement in vaginal atrophy in a meta-analysis of 10 trials and was found to be equally efficacious compared with systemic therapy.¹⁸

Research has shown that low-dose vaginal estrogen is effective and well tolerated for treating vaginal atrophy and has been shown to reduce vaginal symptoms, including dyspareunia and vaginal dryness, and to restore vaginal pH and normal vaginal cytology.^8,19 Local estrogen therapy also offers the benefit of lowered potential for systemic exposure and reduced adverse effects.^1,8

Estrogen for local vaginal application may come in various forms, including estrogen creams, vaginal estradiol tablets, and estrogen rings.^8,20

ESTROGEN CREAMS. Conjugated estrogen vaginal cream in dosages of 0.5–2.0 g has been evaluated in clinical trials and found to be effective in relieving vaginal symptoms.^8,21,22 Treatment with vaginal estradiol cream has also been shown to be effective.²³ Advantages of the cream form include dosing flexibility and lower cost.⁵ Women self-administer vaginal estrogen cream using an applicator; creams are usually applied daily for a few weeks, then two times a week thereafter.⁵

A Cochrane review of local estrogen therapy products found equal efficacy for all products but that use of estrogen creams was associated with increased risk for systemic absorption. Two trials of conjugated estrogen cream showed significant adverse effects of uterine bleeding, breast pain, and perineal pain.¹³ It was also potentially associated with the ability of women to inadvertently use higher doses than recommended.¹³

ESTROGEN TABLETS. Another option for local estrogen therapy is the vaginal estradiol tablet. Vaginal estrogen tablets are self-administered using an applicator; tablets are used daily for the first 2 weeks then twice a week thereafter.⁵ In clinical studies involving estrogen doses as low as 10 μg, estradiol administered by vaginal tablet was shown to be effective in improving vaginal atrophy, relieving vaginal symptoms, decreasing vaginal pH, and increasing maturation of the vaginal and urethral epithelium.³ High vaginal pH (>6.0) has been correlated with high levels of parabasal cells (20% or more), an indicator of an estrogen-deficient epithelium commonly seen in postmenopausal vaginal atrophy.²⁴

Advantages of the estrogen tablet, compared to the cream, include enhanced control of a specific dose, reduced potential for systemic absorption, decreased potential for leakage, and increased adherence compared with vaginal creams.^3,21,25 Study results suggest that the vaginal estradiol tablet and estrogen cream can initially increase systemic estrogen to a small degree when inserted in a very atrophic vaginal epithelium, until the epithelium is thickened (or keratinized). There may be absorption differences according to where local estrogen is placed in the vagina. There is a controlled crossover trial of 10 postmenopausal women that evaluated the site of placement of 17β-estradiol tablets and endometrial safety. When the tablet was placed in the outer one third of the vagina, absorption of estrogen to the uterus was significantly reduced.²⁶

ESTROGEN RINGS. A third alternative for the administration of local estrogen therapy is the estrogen ring. Among estrogen rings, a sustained-release estradiol ring, which releases 7.5 μg estradiol every 24 hours for 90 days, has been shown to be more effective than placebo and as effective as vaginal cream and vaginal tablets in relieving the symptoms of vaginal atrophy and restoring vaginal pH and cytology.^22,27,28

Among the advantages of the vaginal ring treatment option is that it eliminates compliance issues and the risk of endometrial hyperstimulation due to overtreatment.²² In a comparison of the ring and the cream, the ring had better patient adherence and was identified as more acceptable to patients because of comfort, ease of use, and delivery system.¹³ In addition, the estrogen ring offers minimized frequency of application compared with either the cream or tablet form; rings deliver a constant supply of hormone for as long as 3 months, while local estrogen cream or tablets may require at least biweekly application.¹

However, it has been noted that insertion of the ring can be difficult for women with limited vaginal capacity or manual dexterity. In women with pelvic organ prolapse, the product may become dislodged. During intercourse, sexual partners may be aware of the ring, but the ring can be removed if desired for sexual activity.⁹ The vaginal estrogen ring can be inserted by a doctor or the patient, but is usually self-administered and changed every 3 months. Rates of favorable results with low-dose vaginal estrogen are high, with 80% to 90% of women reporting improvement.⁸ The 7.5-µg estradiol ring provides local therapy, but .05 mg/d and .1 mg/d rings are also available for both local and systemic estrogen therapy.⁵

SYSTEMIC ESTROGEN THERAPY

Systemic estrogen therapy is indicated for relief of multiple menopausal symptoms in addition to vaginal atrophy and can improve patient quality of life.²⁹ It may be administered orally, vaginally, or transdermally or by injection or nasal spray.¹³ The hormone progestogen is used to reduce the risk of endometrial cancer associated with systemic estrogen therapy.¹¹

Compared with locally administered therapy, systemic therapy is indicated for relief of vasomotor symptoms associated with menopause as well as prevention of postmenopausal osteoporosis.¹ To reduce the risk associated with systemic hormone therapy, lower doses and less frequent administration may be used.^11,30-32 Although lower doses of estrogen therapies do not require concomitant daily use of progestogen, most clinicians use progestogen either every 3 months, 6 months, or yearly (only with ultra- low dosages) to “challenge” the endometrium if there is any proliferation.^33,34 The other option for monitoring the endometrium is a pelvic sonogram.³¹ When local estrogen therapy is considered solely for vaginal atrophy, no additional progestogen is generally recommended.^8,11,26

Estimates suggest that among women who take systemic hormone therapy, 40% still experience persistent vaginal dryness.⁹ In light of this, and considering the reluctance of many women to discuss vaginal symptoms, clinicians should inquire about persistent vaginal symptoms, as local estrogen therapy may be needed to achieve symptom control.¹¹ Forms of local therapy are summarized in TABLE 1.^1,35-40

Hormonal treatments for vaginal atrophy¹

OPTIMIZING TREATMENT FOR VAGINAL ATROPHY

Postmenopausal women should be evaluated for signs and symptoms of vaginal atrophy, which can have a significant negative impact on patient quality of life.^9,41 As noted, women might refrain from discussing vaginal symptoms with a health-care professional because of persisting cultural taboos about sex, embarrassment over sexual problems, or even self-blame about negative sexual experiences or sexual dissatisfaction.⁸ Therefore, it is important for clinicians not only to initiate conversations about vaginal symptoms with members of at-risk groups, but once a diagnosis of vaginal atrophy is made, also to identify the optimal treatment for that individual patient and to continue to reevaluate the treatment response, medication adherence and compliance, and patient satisfaction with treatment. Individualization and reevaluation is of key importance for successful therapy.

It is recommended that hormone therapy be considered only when an indication for therapy has been clearly identified; contraindications ruled out; and the potential individual benefits and risks adequately discussed with the patient to support informed decision making.¹¹ According to NAMS, a comprehensive history and physical examination are essential prior to initiation of hormone therapy, including assessment of risk factors for stroke, CHD, VTE, osteoporosis, and breast cancer. These results should be discussed with patients prior to initiating therapy. Mammography should be performed according to national guidelines and age but preferably within the 12 months before initiation of therapy.¹¹

Ultimately, the decision of whether to receive systemic hormone therapy depends on a woman’s individual situation and her willingness to accept known risks. Similarly, the acceptance of risk may depend on the reason for consideration of treatment. For example, a woman may be more willing to accept the risk associated with hormone therapy if she is currently experiencing systemic symptoms than she would be if the hormone therapy treatment were intended to lower risk of future possible osteoporotic fractures. Likewise, short-term use of hormone therapy might be more acceptable for a younger woman than long-term use would be for an older woman.¹¹ Extending duration of hormone therapy should also be considered in the context of a woman’s individual risk-benefit profile.¹¹

SUMMARY

Locally administered therapeutic options for vaginal atrophy, including estrogen rings, tablets, and creams, are effective in providing relief of vaginal atrophy symptoms while minimizing risks associated with systemic absorption. Still, for some women, the benefits of systemic therapy—especially when it is for short-term treatment of presenting symptoms—outweigh the risks. Identification of therapy indications, ruling out of contraindications, and discussion of potential individual benefits and risks with a clinician are paramount in determining which treatment option is suitable for each woman.

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