Background for FF #511: Sexual dysfunction is common in patients with serious illness. Up to 90% of patients with cancer (especially gynecologic and breast cancers) experience sexual dysfunction from the underlying illness or treatment-related side effects (1,2). Many patients with serious illness want to discuss their sexual health with their clinicians since sexual symptoms negatively impact relationships, their partner, and their mental health (3,4). Genitourinary symptoms of menopause (GSM) and decreased libido are two common sexual symptoms in patients with serious illness (5). This Fast Fact assimilates the published evidence to provide guidance to clinicians for managing GSM and decreased libido (5).

Definitions and etiology: GSM is a constellation of symptoms caused by a hypoestrogenic state, resulting in changes in urogenital tissues. The hypoestrogenic state is due to the ovaries no longer producing adequate estrogen and progesterone. This condition can result from natural menopause but can also be a result of surgical menopause, chemotherapy, or radiation (6,7). Low libido or decreased sexual desire or arousal is often caused by many factors including medical conditions, psychological factors, dyspareunia, medications, substance use, stress, and/or relationship difficulties.

GSM symptoms are divided into three categories: 

1. Genital (often due to vulvovaginal atrophy): vaginal dryness, irritation, burning, itching, or discharge.
2. Urinary: urgency, frequency, incontinence, recurrent urinary tract infections, discomfort with urination.
3. Sexual: lack of lubrication, low libido, decreased arousal, and dyspareunia (painful intercourse) (6,7).

GSM treatment options: Most of the therapies below can be prescribed by all clinicians. For the less commonly utilized therapies, refractory symptoms, or simply if the clinician ever needs help, referral to a sexual health clinic is recommended. The International Society for the Study of Women’s Sexual Health also has a website (https://www.isswsh.org/) endorsing certain clinicians for GSM care. 

• Psychotherapy and sex therapy is an essential component of GSM treatment not just for the patient, but their significant other too. It is first line treatment for low libido and involves a referral to a licensed sex therapist, psychologist, or licensed clinical social worker (8). It can decrease negative emotional responses to sexual stimulation, improve partner communication, and improve menopause awareness (9). Unfortunately, it is not always covered by insurance.
• Vaginal moisturizers treat daily dryness. They are affordable and include coconut oil or Replense®.
• Vaginal lubricants treat dryness with sexual activity. Water-based lubricants are easy to clean, do not damage condoms or sex toys, but require frequent application and may increase yeast infection risk. Silicone base lubricants are more slippery and longer lasting, do not damage condoms, but are harder to clean and cannot be used with silicone sex toys. Oil-based are less expensive, but difficult to clean and can damage both silicone sex toys and condoms. Avoid petroleum jelly or baby oil.
• Vaginal estrogen can treat essentially all GSM symptoms. It increases blood supply, improves tone, enhances lubrication, normalizes genital pH, and prevents UTIs (6). There are a wide range of preparations, including creams (Estrace, Premarin), rings (Femring), tablets, and inserts (7,10). Of note: low-dose preparations (e.g., Vagifem oral tablets or Estring vaginal rings) may not raise estrogen levels more than placebo (10). Collaborate closely with the patient’s oncologist in patients with hormonally sensitive cancers. Caution is advised for patients on aromatase inhibitors (10).
• Vaginal DHEA (Prasterone 6.5 mg daily vaginal insert) is a precursor to estrogen and androgens. When placed intravaginally, it improves GSM symptoms by increasing local estrogen and androgen levels (11). Abnormal vaginal discharge is a rare side effect. It is more expensive than vaginal estrogen and its safety and efficacy has not been directly compared with vaginal estrogen (11).
• Pelvic floor physical therapy (PT): Patients with dyspareunia naturally tighten their pelvic floor musculature, resulting in muscle hypertrophy and perpetuation of the pain cycle. Pelvic floor PT aids in relaxing and retraining the pelvic floor (12). PTs with specialized training in GSM conditions are available in most communities. The number and type of treatment sessions vary and include biofeedback, manual therapy (including massage and dilator therapy), and trigger point treatment.  Additionally, self-massage of the perineum can be taught to improve perineal elasticity and break down scar tissue.  Vaginal dilators or vibrators may be recommended 2-3 times/week after pelvic surgery or vaginal radiation to break down scar tissue and allow for pelvic examination and penetrative vaginal intercourse.
• Over the counter devices like the Ohnut ring (typically less than $100) reduce pain by limiting the depth of penetration.
• Ospemifene (60 mg daily) is a prescribed selective estrogen receptor agonist/antagonist medication approved for vaginal dryness and dyspareunia. It may decrease the risk of recurrent UTIs too (13). Vasomotor side effects are common (14). The FDA recommends against its use in patients with known or suspected breast cancer (15). Usual cost is around $300 per month.
• Hormone replacement therapy (HRT): The risk to benefit profile of HRT for GSM is complicated and evolving. It is even more so in patients with hormonally sensitive cancer. Consider a referral to a sexual health specialist to weigh HRT risks and benefits in close collaboration with oncology.
• Medications for low libido demonstrate minimal to modest benefits. Their cost can range from $900-$1400 per month and are associated with significant side effects. They are only FDA approved in premenopausal women and include (16):
  • Flibanserin (100 mg at bedtime): Serotonin agonist/antagonist. FDA black box warning for CYP3A4 inhibitors, hepatic impairment, and > 1-2 alcoholic drinks within 2 hours of use (16-17).
  • Bremelanotide (1.75 mg subcutaneous injection): taken 45 minutes prior to sexual activity (18,19). Many contraindications (e.g., heart disease, naltrexone, uncontrolled hypertension).
  • Off label use of testosterone, bupropion and buspirone have demonstrated benefit in sexual desire and satisfying sexual events, but long-term safety and efficacy are unknown (16).

References 

1. Walker LM, Sears CS, Booker R, et al. Development, implementation, and evaluation of a multidisciplinary oncology sexual health clinic in a Canadian cancer care setting. J Cancer Surviv. 2021;15(5):755-766.
2. Vegunta S, Kuhle CL, Vencill JA, et al. Sexual Health after a Breast Cancer Diagnosis: Addressing a Forgotten Aspect of Survivorship. J Clin Med. 2022;11(22):6723.
3. Sporn NJ, Smith KB, Pirl WF, et al. Sexual health communication between cancer survivors and providers: how frequently does it occur and which providers are preferred? Psycho-Oncology 2015;24: 1167–1173.
4. Ussher JM, Perz J, Gilbert E; Australian Cancer and Sexuality Study Team. Perceived causes and consequences of sexual changes after cancer for women and men: a mixed method study. BMC Cancer. 2015;15:268.
5. Esmat Hosseini S, Ilkhani M, Rohani C, et al. Prevalence of sexual dysfunction in women with cancer: A systematic review and meta-analysis. Int J Reprod Biomed. 2022;20(1):1-12.
6. Treatment of Urogenital Symptoms in Individuals With a History of Estrogen-dependent Breast Cancer: Clinical Consensus. Obstet Gynecol. 2021;138(6):950-960.
7. The NAMS 2020 GSM Position Statement Editorial Panel. The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society. Menopause. 2020;27(9):976-992.
8. Goldstein I, Kim NN, Clayton AH, et al. Hypoactive Sexual Desire Disorder: International Society for the Study of Women’s Sexual Health (ISSWSH) Expert Consensus Panel Review. Mayo Clin Pro 2017;92(1):114-128.
9. Carter J, Lacchetti C, Rowland JH. Interventions to Address Sexual Problems in People With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Adaptation Summary. Journal of Oncology Practice. 2017;14(3):173-180.
10. Manson JE, Goldstein SR, Kagan R, et al. Why the product labeling for low-dose vaginal estrogen should be changed. Menopause: The Journal of the North American Menopause Society. 2014;21(9): 911-916.
11. Labrie F, Archer DF, Koltun W, et al. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause. 2016;23(3):243-256.
12. Trahan J, Leger E, Allen M, et al. The Efficacy of Manual Therapy for Treatment of Dyspareunia in Females: A Systematic Review. J Womens Health Phys Therap. 2019;43(1):28-35.
13. Archer DF, Goldstein SR, Simon JA, et al. Efficacy and safety of ospemifene in postmenopausal women with moderate-to-severe vaginal dryness: a phase 3, randomized, double-blind, placebo-controlled, multicenter trial. Menopause 2019;26(6):611-621.
14. Simon JA, Altomare C, Cort S, et al. Overall Safety of Ospemifene in Postmenopausal Women from Placebo-Controlled Phase 2 and 3 Trials. J. of Women’s Health. 2018;27(1):15-23.
15. Cai B, Simon J, Villa P, et al. No increase in incidence or risk of recurrence of breast cancer in ospemifene-treated patients with vulvovaginal atrophy (VVA). Maturitas. 2020;142:38-44.
16. Joffe HV, Chang C, Sewell C. FDA Approval of Flibanserin—Treating Hypoactive Sexual Desire Disorder. N Engl J Med 2016;374(2):101-104.
17. U.S. Food and Drug Administration. FDA label for Addyi (flibanserin). Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022526lbl.pdf  [Last Accessed: August/26/2024].
18. Kingsberg SA, Clayton AH, Portman D, et al Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder. Obstet Gynecol 2019;134(5):899-908.
19. Simon JA, Kingsberg SA, Portman D et al. Prespecified and Integrated Subgroup Analyses from the RECONNECT Phase 3 Studies of Bremelanotide. J Womens Health 2022;31(3):391-400.

Author Affiliations: University of Utah School of Medicine, Salt Lake City, UT (KH, KK, CL); University of Louisville, Louisville, KY (JS).
Conflicts of Interest: Nothing relevant to disclose.
Version History:  Originally edited by Sean Marks MD; first electronically published in May 2025.