How to help patients navigate genitourinary syndrome of menopause

Genitourinary syndrome of menopause (GSM) includes both vulvovaginal and lower urinary tract symptoms resulting from decreased estrogen levels during menopause. Signs and symptoms of GSM include vaginal atrophy, dryness, burning, itching, irritation, dyspareunia, urinary frequency or urgency, and increased risk of urinary tract infections (UTIs). Genitourinary syndrome of menopause is estimated to affect up to 77% of women ¹ ; however, it is often underreported, underdiagnosed, and undertreated despite the availability of safe and effective treatments. Data from a US survey published in 2017 indicated 50% of women experiencing GSM had never used any therapy to address symptoms. ² Barriers to accessing treatment include limited public knowledge of GSM symptoms and treatments; patient and provider hesitancy in discussing the topic; and concerns regarding use of hormone therapies. ^3-5 Symptoms of GSM often persist if untreated and can substantially impair an individual’s health, relationships, sexual intimacy, and quality of life. ^6,7

The Menopause Society (formerly the North American Menopause Society) and the Society of Obstetricians and Gynaecologists of Canada issued separate guidance updates on management of GSM in 2020 and 2021, respectively. ^8,9 This article highlights key information for primary care providers to consider when helping women manage GSM. Through their work with the RxFiles Academic Detailing Program at the University of Saskatchewan in Saskatoon, 2 authors (T.T. and J.V.) also contributed to a detailed summary of menopause therapies for clinicians (Appendix 1, available from CFPlus^* ).

We use the term women throughout this article to remain consistent with the research referenced; however, this term does not apply to all people who experience GSM. Information contained herein is intended to help any person experiencing these symptoms.

Education and GSM screening recommendations

The 2020 Menopause Society guideline recommends GSM education and screening for all perimenopausal and postmenopausal women. ⁸ Incorporating vaginal health screening into routine workflows (eg, during Papanicolaou test appointments for women aged 45 to 69 years), building reminders into documentation templates, and involving interprofessional team members can help facilitate the process and allow for this workload to be shared among primary care providers. In addition, patient education can be enhanced by referring women to reliable up-to-date resources (examples are provided in Box 1 ). ¹⁰

Box 1. Reliable sources of information about GSM for patients.

• Gynaecology Quality Improvement Collaboration: https://gynqi.com

• Menopause Quick 6 assessment tool and treatment algorithm ¹⁰ : https://mq6.ca

• Menopause Foundation of Canada: https://menopausefoundationcanada.ca

• Menopause Society MenoNotes: https://menopause.org/patient-education/menonotes

GSM—genitourinary syndrome of menopause.

Case description

Amy, a healthy 55-year-old woman who became a patient in your clinic this year, presents today for routine cervical cancer screening. She had endometrial ablation at age 50 for heavy menses and has not had vaginal bleeding since. She has always had normal Pap test results, the most recent being 3 years ago. When asked generally, she denies having any concerns.

On examination the vulva appears normal, though you notice Amy has mild discomfort on insertion of the speculum. The vaginal mucosa is pale with a loss of rugae and a few petechiae are noted on the cervix. These findings have you concerned about vaginal atrophy. You complete the Pap test and let her know you will return to the room shortly to discuss her examination. When you return, you obtain permission to ask Amy some sensitive questions. You then mention that during the examination you noted signs of low estrogen in the vagina. You explain this is a common thing in menopause and many women feel symptoms from this change.

Upon specific enquiry, you discover Amy feels dryness and pain during intercourse, though she denies day-to-day symptoms. She would like relief and wants to discuss options available to her.

Nonhormonal vaginal therapies

Nonhormonal vaginal therapies are recommended first-line treatments for women with less severe GSM. ^8,9,11 Nonhormonal vaginal therapies include moisturizers (used regularly as maintenance therapy) and lubricants (used as needed for sexual activity). Various moisturizers and lubricants are available over the counter without a prescription; treatment options are summarized in Table 1 . Vaginal moisturizers require regular application 2 to 3 times per week for at least 4 weeks to allow for an adequate trial. Due to the absence of evidence comparing various vaginal moisturizers, cost and ease of use can guide product selection. A potential barrier to using these over-the-counter products is they are not covered by most private or public drug plans.

Table 1.

Commercially available hormonal and nonhormonal therapies for patients with GSM

CATEGORY	PRODUCT	USUAL (EQUIVALENT) DOSE	COST PER 30 DAYS
Over-the-counter nonhormonal vaginal products	Vaginal moisturizers (gel, ointment, ovules)	Apply vaginally 2-3 times per wk	$16-37 (approximately 10 applications)
	Vaginal lubricants	Apply vaginally as needed prior to sexual activity	$5-10 per tube
Prescription low-dose vaginal estrogen products	Conjugated equine estrogen, 0.625 mg/g vaginal cream	0.5-2 g vaginally daily for 2 wk, then decrease to 1-3 times per wk	$10 ($34 per 30 g tube)
	Estrone, 1 mg/g vaginal cream	0.5-2 g vaginally daily for 2 wk, then decrease to 1-3 times per wk	$10 ($48 per 45 g tube)
	Estradiol-17β, 2 mg vaginal ring (releases 7.5 μg per day)	1 ring vaginally every 90 days	$32 ($96 per ring)
	Estradiol-17ß, 10 μg vaginal tablet	1 tablet vaginally daily for 2 wk, then decrease to 1-3 times per wk	$30-70
	Estradiol-17ß, 4 μg or 10 μg vaginal softgel	1 softgel vaginally daily for 2 wk, then decrease to 1-3 times per wk	$27-58
Other prescription products	Ospemifene, 60 mg oral tablet	1 tablet orally daily with food	$66
	Prasterone, 6.5 mg vaginal ovule	1 ovule vaginally daily	$58

GSM—genitourinary syndrome of menopause.

Back to the case

After reviewing general vulvovaginal hygiene measures, you discuss the use of lubricants and moisturizers, which Amy is open to trying.

She returns 4 weeks later for follow-up. After trying 2 products she found at her local pharmacy (a twice-weekly vaginal moisturizer with hyaluronic acid and a silicone-based lubricant used as needed for intercourse), she noted some improvement but continues to feel bothersome dryness. You discuss vaginal estrogen options with her.

Vaginal estrogen therapies

Low-dose vaginal estrogen therapies are recommended for women with moderate-to-severe GSM or recurrent UTIs or for individuals whose symptoms are not adequately addressed by an initial trial of a nonhormonal moisturizer. ^8,9 Low-dose vaginal estrogen therapies are highly effective for patients experiencing GSM, with improvements in symptom severity of 60% to 80% noted across a number of trials. ¹ Several prescription vaginal estrogen products are available in Canada, as described in Table 1 . Apart from vaginal rings, all products are prescribed with an initial loading dose (ie, daily administration for 2 weeks) followed by maintenance dosing (ie, 1 to 3 times per week based on symptom control). All products are similarly effective. ⁹ Initial benefits of vaginal estrogen may be seen within the first few weeks of use; full effects are typically noted after 12 to 16 weeks of regular use. Vaginal estrogen should be continued at the lowest effective dose for as long as benefit is noted and may be continued indefinitely. Discontinuation leads to the vaginal mucosa returning to a hypoestrogenic state, often resulting in symptom recurrence.

Choice of product depends largely on patient preference using a shared decision-making approach. Box 2 summarizes considerations that should inform choices about vaginal estrogen products.

Box 2. Factors to consider when choosing between low-dose vaginal estrogen products.

• Estradiol-17β vaginal softgels may be appealing for individuals concerned about exposure to hormone therapy, as they are available in an ultra-low-dose format (4 μg of estradiol-17β), unlike other vaginal estrogen products.

• Estradiol-17β vaginal softgels are inserted manually without an applicator device. This contrasts with estradiol-17β vaginal tablets, which are packaged with a single-use applicator, making this option unacceptable to environmentally conscious patients.

• Vaginal tablets, softgels, and vaginal rings may be less messy options; however, vaginal creams may be used preferentially for women with substantial atrophy, as they can be applied externally to promote vaginal tissue healing prior to insertion.

• Vaginal estrogen creams require the user to prepare the dose. This allows for dosing flexibility, which can be beneficial in some situations (eg, tapering to the lowest effective dose), but it may also have unintended consequences (eg, use of higher-than-recommended quantities).

• Estrone vaginal cream (which is unscented) may be preferred over conjugated equine estrogen vaginal cream (which is rose scented) and may be less irritating to vaginal mucosa.

• Estradiol-17β vaginal rings may be favoured from a convenience perspective as they require infrequent self-insertion by the patient or health care provider every 3 months.

Women receiving systemic hormone therapy for vasomotor symptoms (eg, oral or transdermal) may not experience adequate relief of GSM due to insufficient concentration of estrogen in urogenital tissue. ¹² To address this, low-dose vaginal estrogen therapy can be used safely in addition to systemic hormone therapy to provide targeted management of local symptoms.

Recurrent UTIs

Vaginal estrogen therapy is a useful treatment option for postmenopausal women experiencing recurrent UTIs (commonly defined as 3 or more UTIs in 1 year or 2 or more UTIs in 6 months). ¹³ In a meta-analysis of 8 randomized controlled trials (RCTs) published in 2020, various vaginal estrogen products were associated with a significant reduction in the risk of recurrent UTIs compared with placebo over 6 to 12 months in postmenopausal women (relative risk=0.42, 95% CI 0.30-0.59; number needed to treat=7). ¹⁴ It is important to note the meta-analysis had several limitations, such as inclusion of several trials with bias due to missing outcomes. In addition, the benefit was observed only with vaginal estrogen and did not extend to systemic estrogen preparations (eg, oral or transdermal).

Back to the case

You provide Amy with education about the benefits of vaginal estrogen and outline various available products. Since your initial visit she has read more about GSM. One website discussed the link between estrogen and breast cancer, which has her concerned.

Systemic estrogen exposure and safety of vaginal estrogen preparations

Systemic absorption of low-dose vaginal estrogen is minimal, with plasma estradiol levels remaining in the normal postmenopausal range (ie, <184 pmol/L). ^8,15-17 Among commercially available low-dose products (described in Table 1 ), vaginal tablets, softgels, and rings appear to have the lowest systemic absorption. ¹⁸ Women with substantial vaginal atrophy may experience some systemic absorption early in the treatment course due to atrophied vaginal tissue; however, this decreases with continued use as urogenital tissues begin healing. ^8,19 Overall, all low-dose vaginal estrogen preparations are minimally absorbed and do not necessitate coprescription of a progestogen for endometrial protection. ^8,18,20

Low-dose vaginal estrogen safety is supported by several RCTs and long-term observational studies. A Cochrane review published in 2016 (N=30 RCTs, n=6235) reported no significant differences in endometrial hyperplasia related to use of low-dose vaginal estrogen formulations. ²⁰ Furthermore, in an 18-year prospective cohort study of postmenopausal women (n=53,797) in the Nurses’ Health Study, those using low-dose vaginal estrogen (n=896) showed no increased risk of cardiovascular disease, hip fracture, or cancer (breast, endometrial, ovarian, or colorectal). ²¹

Despite these overwhelming safety data, low-dose vaginal estrogen products still carry the same Health Canada–mandated black-box warnings as systemic estrogen products, advising consumers of risks including coronary artery disease, stroke, venous thromboembolism, breast cancer, and endometrial cancer. ²² These warnings are not reflective of current safety data and can cause undue distress in patients. ²³ Clinicians can proactively inform patients about whether such warnings are relevant when prescribing low-dose vaginal estrogen to avoid unnecessary alarm.

Back to the case

You thank Amy for bringing up her concerns and note there is a lot of misinformation out there. You reassure her vaginal estrogen is safe and very little to no estrogen is absorbed into the blood stream at doses used in the vagina. You explain vaginal estrogen has not been associated with cancer or heart disease, but based on Health Canada requirements all estrogen products are labelled the same. She therefore might see a black-box warning of risks on vaginal estrogen products, but this warning does not reflect what studies tell us about vaginal estrogen.

Amy says this is helpful to know. She mentions she has seen social media posts about newer options beyond vaginal estrogen that might be applicable to her situation, and she asks you for additional information.

Newer pharmacologic therapies

Ospemifene and prasterone are the latest pharmacologic developments available for the treatment of patients with GSM. Ospemifene is a selective estrogen receptor modulator that has agonistic effects on vaginal epithelium and bone, partial agonistic effects on the endometrium, and antagonistic effects on other tissues, including breast. ²⁴ Prasterone is a sex steroid precursor that is converted to estrogens and androgens intracellularly. ²⁵ It acts locally in the vaginal endothelium as an estrogen and androgen agonist. Although no head-to-head trials exist comparing these newer treatments to low-dose vaginal estrogen, they perform similarly in placebo-controlled clinical trials. ^25,26

Ospemifene is unique in that it is an oral tablet taken once daily with food. ²⁷ As such, it may be advantageous for women with substantial dexterity concerns or for those who prefer to avoid vaginal administration. A limitation of ospemifene is it can cause vasomotor symptoms as a side effect. Prasterone is a vaginal ovule administered once daily. ²⁸ The more frequent maintenance dosing compared with vaginal estrogen products (daily vs 1 to 3 times per week) may be unfavourable for some.

Overall, there are limited reasons to favour these newer agents over more cost-effective low-dose vaginal estrogen alternatives. Ospemifene and prasterone are commonly reserved as third-line treatment options in women who fail or are intolerant of a trial of nonhormonal moisturizers or low-dose vaginal estrogen.

Back to the case

After discussing her options, Amy decides to use the estradiol-17β vaginal ring because of the convenience of infrequent administration.

When you see her a few months later for another concern, you check in about her estradiol-17β vaginal ring. She thanks you sincerely; her vaginal discomfort and dyspareunia have resolved completely. You remind her that to maintain the benefits, vaginal estrogen products need to be used continuously and are safe to use as long as needed.

Amy says she has been thinking about the information you provided about menopausal symptoms and the benefits of vaginal estrogen, and she notes her 80-year-old mother struggles with frequent bladder infections. Her mother is otherwise healthy but had breast cancer 15 years ago. Amy asks whether vaginal estrogen may be an option for her mother. You explain vaginal estrogen can be used at any age. You recommend having her mother consult her regular primary care provider for help in deciding whether it is right for her.

Treatment considerations for breast cancer survivors

Nonhormonal treatments—including vaginal moisturizers, lubricants, and pelvic floor physiotherapy—should be considered first-line treatments for women with a personal history of breast cancer. If symptoms persist despite optimizing nonhormonal treatments, low-dose vaginal estrogen (preferentially vaginal tablets, softgels, or rings over vaginal creams) may be considered on an individual basis in consultation with the patient’s oncologist, where possible. ^8,9

Clinical trials are ongoing to establish safety of vaginal hormonal products in breast cancer survivors ²⁹ ; however, only observational data currently exist to support this recommendation. Several recently published, large, population-level studies indicate low-dose vaginal estrogen does not affect life expectancy in women with a history of breast cancer. ^30-33 Furthermore, data suggest women taking tamoxifen who are treated with low-dose vaginal estrogen do not have an increased risk of breast cancer recurrence. ^30,33 In contrast, for those taking aromatase inhibitors (eg, letrozole, anastrozole), treatment with low-dose vaginal estrogen was associated with a higher risk of breast cancer recurrence but did not appear to affect mortality. ^30,33 The observational methodology of these studies imparts several limitations; however, in absence of prospective clinical trials, treatment decisions can be informed by careful interpretation of these data using a shared decision-making approach with the patient and their health care team.

Although contraindicated according to product labels, off-label use of low-dose vaginal estrogen in women with a history of breast cancer is accepted by the Society of Obstetricians and Gynaecologists of Canada and is commonly done in clinical practice. ³⁴

Ospemifene and prasterone are currently not recommended for use in this patient population, as they have not been adequately studied. ⁸

Nonpharmacologic therapies

Nonpharmacologic options are also available to enhance symptom relief.

After menopause the vulva and vagina are more vulnerable to subtle irritants. Consider providing education on vulvovaginal hygiene, including avoiding use of perfumed products and soaps in the genital area; wiping from front to back; avoiding toilet paper made of recycled paper or preferably cleaning only with water using a squirt bottle; and avoiding vaginal douches. ^35,36

Regular sexual touch can help by increasing vaginal blood flow and secretions, whether with a partner or alone, or with or without a device (eg, vibrator). ⁸

Physical changes associated with GSM include narrowing of the introitus and shortening of the vagina; women can use vaginal dilators to stretch the vagina at the direction of a physician or physiotherapist. ⁸

Finally, dyspareunia from dryness can lead to secondary vaginismus. Many women, especially those with a long-standing history of dyspareunia, would benefit from assessment by a pelvic floor physiotherapist and from pelvic floor exercises. ⁸

Conclusion

Genitourinary syndrome of menopause is often underreported, underdiagnosed, and undertreated. By providing education and inquiring about GSM symptoms, clinicians can help patients make informed decisions about treatment options for managing symptoms effectively and ultimately improving quality of life.