Breast Cancer

Dyspareunia and vaginal dryness after breast cancer treatment

Clinical Assistant Professor, Program in Women’s Oncology

Assistant Professor, Obstetrics and Gynecology and Medicine

Co-Directors, Center for Sexuality, Intimacy & Fertility, Women and Infants Hospital of Rhode Island, Providence, Rhode Island

Dr Wiggins reports no commercial or financial interests or other relationships with any company that provides medically related services.

Dr Dizon reports that he has served as a consultant to Genentech and Bristol-Myers Squibb and served on the speakers’ bureau of Ortho Biotech.

The success we have had in treating breast cancer means that 2.5 million women live beyond diagnosis and treatment, facing daily changes in their quality of life. Sexual problems are reported to occur in up to 90% of breast cancer survivors, 50% of whom experience chronic difficulties.¹ The most common sexual complaints are dyspareunia and vaginal dryness,² the management of which can be challenging due to the severity of the symptoms and the complicated hormonal milieu of the disease and its treatment. This article describes the vaginal changes that occur in breast cancer patients and the therapeutic use of vaginal moisturizers and lubricants.

Cancer treatments and their sexual side effects

Approximately 26% of women diagnosed with breast cancer are premenopausal¹; many will receive systemic chemotherapy and/or hormonal therapy that result in significant changes to their normal sexual function. Postmenopausal women who receive chemotherapy and/or hormonal therapy may notice worsening of menopausal symptoms, including vaginal atrophy and dryness.³

Chemotherapy: Menopausal symptoms, skin toxicity

Chemotherapy can abruptly and permanently reduce ovarian reserve and induce menopausal symptoms. Dyspareunia coincides with vaginal dryness, with the potential to initiate sexual avoidance patterns and behaviors that exacerbate the problem: Regular sexual activity has been shown to improve vaginal atrophy by stimulating blood flow to the area.⁴

Chemotherapy can worsen dyspareunia and mucositis beyond the menopausal symptoms patients often experience. Skin toxicity can occur with chemotherapy drugs, causing vaginal mucosal erythrodysesthesia (similar to mucosal changes noted in the lining of the mouth and gastrointestinal tract) that results in vaginal burning, inflammation of mucosal tissue, and erythematous changes to the vaginal vault and perineum.⁵

Hormone therapies: Disparate effects on urogenital tissue

Hormonal therapies for breast cancer treatment include tamoxifen, raloxifene, and aromatase inhibitors (AIs). These agents have anti-estrogenic properties within the breast but exhibit different end effects in urogenital tissue.

Tamoxifen. The increased risk of endometrial hyperplasia and cancer after treatment with tamoxifen is well known and commonly discussed with patients. However, clinicians often fail to mention tamoxifen’s ovarian and vaginal side effects.

In postmenopausal women, tamoxifen acts as a weak estrogen in the ovaries, uterus, and vaginal epithelium. Premenopausal women treated with tamoxifen often experience varying endometrial changes: dysfunctional bleeding, oligomenorrhea, and amenorrhea.⁶ Women with regular cycles prior to tamoxifen therapy are at increased risk for ovarian cysts and elevated serum estrogen levels.⁷ Tajima et al reported on the antiestrogenic effects seen in the vaginal epithelium of premenopausal women being treated with tamoxifen for infertility.⁸

Raloxifene. Originally approved for the treatment of postmenopausal osteoporosis, raloxifene was approved in September 2007 for breast cancer risk reduction.⁹ Raloxifene’s effect on vaginal mucosa suggests an agonistic influence. In postmenopausal women, raloxifene is not associated with adverse vaginal symptoms¹⁰ and does not affect sexual function.^11,12 There are no conclusive data about the relationship of sexual function and raloxifene in premenopausal women or in younger postmenopausal women who may be experiencing menopausal symptoms.

A placebo-controlled, randomized study evaluated postmenopausal women with signs of vaginal atrophy who were using raloxifene to determine whether symptoms improved with either low-dose vaginal estrogen or a nonhormonal vaginal moisturizer; both were found to be effective treatments.¹³

Aromatase inhibitors. Postmenopausal women with estrogen receptor (ER)-positive breast cancer are often offered AIs (anastrozole, letrozole, exemestane) as first-line treatment or switched to AIs after 2 to 3 years of tamoxifen. AIs inhibit estrogen synthesis, resulting in extremely low circulating estrogen levels. Breast cancer patients report more vaginal dryness, dyspareunia, and loss of sexual interest with AI-only treatment than with tamoxifen alone.¹⁴

Assessing estrogen stimulation in the vagina

The evaluation of the breast cancer patient who presents with dyspareunia and vaginal dryness should include a pelvic exam and thorough history.

The vagina is lined by stratified squamous, nonkeratinized epithelium containing estrogen receptors.¹⁵ The epithelium is multilayered, and stimulation by estrogen maintains the epithelial collagen levels, helping vaginal thickness and elasticity and optimizing vaginal blood flow. In the presence of estrogen, the nonkeratinized, stratified squamous cells of the vagina are rugated, plump, and glycogen rich.¹⁶ Lack of estrogen causes thinning of the vaginal epithelium, vaginal dryness, and inflammation of mucosa; this condition is variously called atrophic vaginitis or urogenital or vaginal atrophy.

Several microorganisms exist in the vagina, the most predominate of which is Doderlein’s lactobacillus. Increasing vaginal pH during menopause is detrimental to lactobacilli, tipping the ecobalance of the vagina.¹⁷ The normal pH of the vagina is between 3.8 and 4.5; in menopause, the pH is higher than 4.5. Although there is no evidence in the literature that chemotherapy affects vaginal pH directly, it does cause atrophic vaginitis, which changes vaginal pH.

Another index of the hormonal stimulation of vaginal epithelium is the maturation index value, which is obtained by cytologic evaluation of a smear from the proximal lateral vaginal wall (SIDEBAR). Estrogen stimulates the development of superficial squamous cells; a shift to the left is associated with vaginal atrophy.¹⁸

Physical examination of the vagina should include evaluation of rugae, color, presence or absence of petechiae, elasticity (mucosal thinning), pain to touch, and dryness. A descriptive assessment of the vaginal mucosa is in the TABLE.¹³

Finally, a thorough history should include current and previous disease therapies, stage and ER/PR status, description of past and present sexual function, medications, and a complete medical history. It is necessary to perform a psychosocial and relationship assessment because the general distress of a cancer diagnosis, depression, anxiety, body dysmorphism, and relationship changes can contribute to sexual dysfunction.^19,20

Clinical Assessment of the Vagina

Product sensitivity: influential factors

Breast cancer patients who experience vaginal atrophy or irritation from chemotherapy, hormonal interventions, or menopausal changes may have varying sensitivity to vaginal products. Nonhormonal vaginal moisturizers and lubricants are helpful in optimizing hydration of the vaginal mucosa and relieving atrophic symptoms; however, little clinical research has been published in this area.

An animal model using slugs has been validated to test mucosal irritation in human mucosal membranes. A recent study using the slug mucosal irritation assay determined that product osmolality was an important component to mucosal tolerability. The iso-osmotic lubricant (Pre-Seed) caused no changes and, therefore, was the best tolerated. The hypo-osmotic lubricant (Femglide) caused negative mucus production, thereby decreasing natural response. Two moderately hyperosmotic lubricants (Replens, K-Y jelly) induced mild and moderate irritation, respectively. The highly hyperosmotic lubricant (Astroglide) resulted in severe irritation and tissue damage.²¹

For clinicians, the key point of this study is that not all “water-based” products are the same. If a patient cannot tolerate one product, there are similar products with different properties available.

Review of available lubricants and moisturizers

Replens is a polycarbophil-based vaginal moisturizer that contains purified water, glycerin, mineral oil, hydrogenated palm oil, and sorbic acid. This nonhormonal alternative for vaginal atrophy has been shown to decrease dyspareunia, improve vaginal dryness, and increase the maturation index, when used regularly.^22-24 The active ingredient is a bioadhesive polymer that is water swellable but not water soluble, which binds directly to the vaginal epithelium. The hydrating property restores the vaginal pH to premenopausal levels and reduces the incidence of vaginal dryness, itching, and irritation.²⁵

Two studies have looked at the efficacy of Replens for breast cancer patients for the treatment of vaginal atrophy and found Replens to be as effective as conjugated estrogen vaginal cream.^26,27

K-Y Brand includes a complete line of products for men and women, ranging from moisturizers to lubricants. K-Y Liquibeads and K-Y Silk-E are water-based moisturizers. The sexual lubricant selection ranges from traditional products to warming gels. Most recently, the manufacturer introduced K-Y Yours+Mine, sexual enhancing lubricants for both partners.

Vagisil has a pH testing kit and products to treat vaginal itching and dryness with a variety of creams, wipes, powders, and lubricants.²⁸

YES comes from England. It is a water-based vaginal moisturizer and personal lubricant, derived from plants (flax extract, guar, locust bean, and xanthan gum).²⁹

Astroglide products are FDA-approved and include a wide variety of moisturizers and lubricants.³⁰

Pre-Seed has been marketed to couples who need lubrication that does not inhibit fertility.

Femglide is sugar free, which may appeal to patients with diabetes. In contrast, most water-based lubricants contain glycerin and increase the risk of yeast infections with topical use. In patients with vaginal atrophy, this risk may be further elevated.

SIDEBAR

Pilocarpine has been shown to be effective in a Phase III study of vaginal dryness in Sjögren syndrome. These findings provoked interest in use of pilocarpine after chemotherapy. A pilot study using oral pilocarpine (5 mg TID) in women who developed amenorrhea and vaginal dryness following chemotherapy found that pilocarpine stimulated mucus and other moisture-producing cells in vaginal mucosa and muscularis. Marked clinical improvement in vaginal dryness was noted among study participants.³¹

Zestra is made of biological ingredients and naturally stimulates the body’s own sensory nerve conduction, heightening sexual sensation and pleasure. It is not a vaginal lubricant, but it does help with lubrication. Preservative-free Zestra is composed of borage seed oil, evening primrose oil, angelica extract, coleus extract, vitamins C and E. Zestra has also been shown to improve sexual function in menopausal women.³²

Beyond lubricants: Topical anesthetics

In addition to use of vaginal moisturizers and lubricants, topical anesthetics may be helpful to patients with significant dyspareunia. Overnight 5% lidocaine ointment has not been studied in breast cancer patients with dyspareunia, but it has been helpful in women with vulvar vestibulitis.³³ Topical gabapentin cream (6% compounded formula, applied TID) is useful in the treatment of localized and generalized vulvodynia,³⁴ and theoretically may be helpful for women with vaginal mucosal erythrodysesthesia after chemotherapy.

Issues in the use of estrogen

Use of low-dose vaginal estrogen therapy for breast cancer patients with vaginal dryness and dyspareunia is debatable. Not all breast cancers are hormone positive; however, most women with breast cancer are aware of the effect of hormones on breast disease, and many may feel uncomfortable using estrogen treatments. In a study group of 250 women previously diagnosed with breast cancer, 78% would not consider use of systemic estrogen for the relief of menopausal symptoms, primarily out of fear that estrogen could contribute to breast cancer recurrence.³⁵ However, sexually active breast cancer survivors were more comfortable using local estrogen treatment for urogenital symptoms in a monitored clinic setting.³⁶

Topical local estrogen preparations are preferred to systemic therapy for the relief of vaginal dryness and dyspareunia; these formulations result in less systemic absorption. Vaginal estrogen should be considered for a breast cancer patient if significant vaginal atrophy, dryness, and dyspareunia persist despite nonhormonal interventions. Vagifem tablets, Estring (silicone ring), and topical estrogen creams are the most common vaginal estrogen treatments. Local therapies improved the maturation index, lubrication, and symptoms in about 4 weeks.³⁷ Vagifem and Estring are preferred over vaginal estrogen creams by patients, and both agents have demonstrated a 90% improvement of atrophic symptoms.^38,39

When beginning local estrogen therapy, the circulating serum level of estrogen may rise, due to the weakened skin integrity of the fragile atrophied vaginal mucosa. Elevated circulating estrogen may be problematic to women receiving AI therapy; these patients should be closely monitored.⁴⁰ One randomized trial compared 10-mcg and 25-mcg doses of Vagifem for the treatment of atrophic vaginitis. Both preparations relieved symptoms, decreased vaginal pH, and increased the maturation index. Greater improvement was seen with the higher dose, but for the breast cancer patient with sexual dysfunction from atrophic changes, it may be preferable to begin with the 10-mcg tablet.⁴¹

Conclusion

It is estimated that 2.5 million women in the United States are breast cancer survivors, and the 5-year survival rate is 90%. Sexual problems, particularly dyspareunia and vaginal dryness, are very common following breast cancer diagnosis and treatment.¹ Patients may benefit from the wide variety of nonhormonal lubricants and moisturizers or topical anesthetics. In some cases, local estrogen can be an alternative option, although patients must be carefully monitored, and many may not be comfortable with this approach.

Sexuality, Reproduction & Menopause ©2008 Quadrant HealthCom Inc.