Abstract
The Clinical Update series is intended to help busy clinicians stay up to date with recently published important and potentially practice-changing articles on topics pertinent to the care of women. In this update on sexual health, we review studies on use of vaginal dilators for vaginal stenosis in gynecologic cancer survivors, sexual dysfunction in transgender people, as well as studies evaluating the effect of physical activity and infertility on female sexual health.
Vaginal Dilators for Vaginal Stenosis in Gynecologic Cancer Survivors
Martins J, et al. Topical estrogen, testosterone, and vaginal dilator in the prevention of vaginal stenosis after radiotherapy in women with cervical cancer: A randomized clinical trial. BMC Cancer 2021;21(1):682.
Charatsi D, et al. Vaginal dilator use to promote sexual wellbeing after radiotherapy in gynecological cancer survivors. Medicine (Baltimore) 2022;101(4):e28705.
What we know
Vaginal stenosis (VS) is a major complication of radiotherapy (RT) in gynecologic cancer survivors, affecting 79% of cervical cancer survivors and 67% of endometrial cancer survivors. 1 Sexual dysfunction because of VS affects up to 88% of cervical cancer survivors and 91% of endometrial cancer survivors. 1 There is no consensus on the ideal treatment, but vaginal dilator therapy (VDT) and vaginal estrogen (VE) are two globally accepted therapies for VS. VDT facilitates early separation of the vaginal walls, prevents adhesions, and stimulates vaginal epithelial cell growth, but it poses a risk of vaginal wall injuries. 2 Estrogen is also thought to promote vaginal epithelial cell growth, but it is best avoided in stage III and IV endometrial cancer due to the recurrence risk. In addition, pelvic RT can reduce estrogen and androgen receptor protein expression in the vaginal mucosa, compromising the effectiveness of VE. 2 Although VDT and VE are widely used treatment options for VS, there are no guidelines that identify the optimal time to start VDT, and it is unknown how VDT compares with other potential interventions for improving VS, including VE.
Study results
Randomized control trial
In the trial by Martins et al, a total of 209 women (aged 18–75 years) receiving first-time external beam radiotherapy (EBRT), brachytherapy (BT), or both for cervical cancer stage I to IIIB were randomized to 4 treatment groups: lubricant gel (control group; n = 73), VE (conjugated estrogen cream 0.625 mg/g; 1 g thrice a week; n = 69), VDT (n = 31), and vaginal testosterone (testosterone propionate cream 300 mcg/mL; 1 mL thrice a week; n = 36). The mean EBRT dose was 45.29 ± 2.43 Gy in the pelvis and 14.27 ± 0.68 Gy in the parametrium, and the mean BT dose was 26.65 ± 3.22 Gy. The women were evaluated at baseline upon completion of RT and then for follow-up at 4, 8, and 12 months. VS was assessed at each visit by pelvic examination according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and by change in the vaginal volume using graduated cylinders. CTCAE is a descriptive terminology that provides a severity scale for VS. 3 Grade 0 is the absence of VS; grade 1 is vaginal narrowing and/or shortening not interfering with function; grade 2 is vaginal narrowing and/or shortening interfering with function (e.g., dyspareunia); and grade 3 is the total occlusion of the vaginal canal that cannot be surgically corrected. At the end of the 12-month follow-up, nearly all participants (92.3%) experienced a reduction in vaginal volume. The mean reduction in vaginal volume was 25.5% for the total group, with similar worsening in all four groups, and no statistical difference among the groups throughout the 12-month follow-up period.
In addition, at the end of the 12-month follow-up, VS grade worsened in all groups, except the VDT group, where it stayed stable despite the reduction in the vaginal volume. At baseline, most of the women had grade 1 or grade 2 VS (73.8%), with the rest having no stenosis. At the end of 12 months, 95.8% of the participants had grade 1 or grade 2 VS, with the rest having no stenosis.
Prospective observational study
Charatsi et al studied 53 women with a history of cervical or endometrial cancer who were receiving RT (radical or adjuvant EBRT and/or BT). Most patients (85%) underwent EBRT and received the standard adjunctive EBRT dose (45–50.4 Gy) over 25–38 sessions. Similarly, all patients, except for one, received high dose BT. The women were evaluated at the end of RT and at 3, 6, and 12 months after completion of RT. At each visit, VS was assessed by a pelvic examination according to the CTCAE version 5.0 criteria, and the participants completed a 20-item validated questionnaire to assess sexual and vaginal problems in patients with gynecologic cancers (Sexual Function Vaginal Changes). 4 The participants were educated on the use of VDT along with a lubricant twice a week for a total of 10 minutes per session. They were also contacted once a month to ensure compliance and to address any difficulties associated with VDT. All participants started with VS grade 2 or greater according to the CTCAE version 5.0. Throughout the year of study, the VS grade decreased and the vaginal dilator (VD) size that could be comfortably inserted increased gradually.
After 12 months of VDT, all patients with initial grade 3 VS showed a final grade 2 VS, and 65.8% of those with initial grade 2 VS improved to grade 1 VS. Nearly 80% of the participants starting with the first size VD were using third size VD after 12 months. Women also reported decreased dryness, pain, and bleeding during intercourse; 60.9% did not feel their vaginas were small during intercourse, and 47.7% were satisfied with their sexual lives. The study also assessed the impact of the timing of VDT on the final grade of VS. The participants starting VDT within 3 months of completing RT, and not any later, had statistically significant improvement in VS.
What this changes or adds
Despite being a common complication that affects sexual function and quality of life, RT-induced VS is poorly studied. The American Cancer Society recommends VDT or sexual intercourse thrice per week to protect against VS. 2 The randomized clinical trial described above is the first to describe superiority of VDT over other treatment modalities in terms of preventing VS progression. While vaginal volume reduction still occurred with VDT, it was not accompanied by worsening of VS and sexual function, especially if started within 3 months of completing RT. The findings highlight the responsibility of clinicians to adequately counsel their patients about the effectiveness of VDT and the time sensitivity of this treatment option. VDT should be initiated as soon as feasible upon completion of radiation treatments, ideally within the 3-month window.
Sexual Dysfunction in Transgender People
Mattawanon N, et al. Sexual dysfunction in transgender people: A systematic review. Urol Clin N Am 2021;48:437–460.
What we know
Despite the increasing awareness and visibility of transgender care in medical practice, there continue to be important knowledge gaps. As an example, there is limited research on sexual dysfunction in these individuals, and standard diagnostic criteria do not exist. Many transgender and gender nonbinary people may receive gender affirming hormone therapy (GAHT) or undergo gender-affirming surgery (GAS) such as a hysterectomy, chest reconstruction, phalloplasty, or creation of a neovagina depending on their goals. 5 Both GAHT and GAS may modify the sexual response physiology via multiple mechanisms, 6 but the impact of these treatments on overall sexual health in transgender people is not well understood.
Study results
This systematic review searched all studies on sexual function, satisfaction, and dysfunction in transgender adults after initiation of GAHT and/or GAS, with a focus on desire, arousal, orgasm, pain, and sexual behaviors, and ultimately included 44 studies.
Transgender men
Eight studies evaluated sexual desire in transgender men, most of them specifically evaluating the effects of GAHT and GAS on sexual desire. Overall, there was an increase in sexual desire after GAHT (testosterone) in transgender men, which increased within months of initiation of treatment. Route of testosterone administration did not impact the outcome. Studies on sexual desire after GAS in transgender men were small, and results were mixed. Four studies evaluated sexual arousal in transgender men and overall found improved sexual arousal after GAHT, and mixed results after GAS. In the seven studies that evaluated orgasm in transgender men, there were mixed results, and only one study looked at the impact of GAHT on orgasmic function (no impact). Only 2 studies evaluated sexual pain in transgender men, describing an occurrence of pain with erectile prosthesis in a small study, and a 12% estimate of sexual dysfunction caused by pain (in 211 participants).
The studies evaluating sexual behaviors and activity found positive effects of GAHT and GAS on masturbation and sexual activity; results were mixed regarding the effect of these treatments on sexual orientation (some found no effect, others found that up to 22% of participants changed their sexual orientation after GAHT/GAS). The six studies evaluating sexual satisfaction demonstrated improvement after GAHT/GAS. Body satisfaction and improved body image, particularly after GAS, correlated positively with indicators of sexual behavior.
Transgender women
Sexual desire in transgender women after GAHT or GAS was evaluated in 12 studies. In most, a reduction in sexual desire was noted after GAHT (estrogen and antiandrogen therapy), but it was not reported to be distressing. Many of the studies showed that the reduction in desire was transient and ultimately returned to baseline. The studies were mixed for desire after GAS, and it appears that the type of surgery had different effects on sexual desire. Orchiectomy decreased desire, but vaginoplasty and breast augmentation did not impact sexual desire. The eight studies evaluating sexual arousal found that GAHT and GAS did not negatively impact sexual arousal in transgender women for the most part. Two studies showed a positive impact of GAS on sexual arousal, although dissatisfaction was reported due to lack of vaginal lubrication after GAS.
As for orgasm, 22 studies in transgender women found mixed results regarding orgasm after GAHT and GAS. One study showed that the prevalence of orgasmic dysfunction decreased from 46.7% to 29.2% after GAHT. Overall, for transgender women, the effects of GAS on orgasm remained inconclusive. Eleven studies evaluated sexual pain in transgender women and found mixed results. Pain appeared to occur more commonly in transgender women with a neovagina compared to those without a neovagina. Masturbation and sexual fantasy frequency decreased for transgender women after GAS, but neoclitoral sensation was reported to be good by the cited studies. Like in transgender men, there was a positive effect on satisfaction in sexual functioning after GAS. However, compared to cisgender women, transgender women scored lower overall on the Female Sexual Function Index (FSFI), indicating poorer sexual function.
What this changes or adds
Providing evidence-based and culturally agile care to transgender people is critically important, but the lack of data regarding sexual health outcomes after GAHT and/or GAS has significantly limited the ability to do so. This review summarizes the current literature as it relates to sexual functioning in transgender women and men to aid clinicians in counseling patients, particularly those who are interested in pursuing GAHT or GAS. However, the quality of the evidence included in the review is limited by the small size of the studies and heterogeneity of the tools for assessment of sexual functioning. Additional large prospective studies utilizing standardized tools to measure sexual function in transgender people are needed.
Physical Activity and Female Sexual Dysfunction
Maseroli E, et al. Physical activity and female sexual dysfunction: A lot helps, but not too much. J Sex Med 2021;18:1217–1229.
What we know
Physical activity (PA) has numerous health benefits, including lowering the risk of cardiovascular disease, diabetes, and cancer. 7 PA has also been shown to have a favorable effect on male sexual function. 8 However, the impact of PA on female sexual function has not been adequately studied. The existing evidence is limited to few population-based studies, performed in middle-aged community dwelling women. In general, there seems to be a suggestion of poorer sexual function in women with lower PA level, 9,10 but there have been no systematic studies evaluating this association. The aim of the current study was to evaluate the association between PA levels and sexual function in pre- and postmenopausal women.
Study results
This was a retrospective study of 322 pre- and postmenopausal heterosexual women who were evaluated for sexual dysfunction in a multidisciplinary university hospital in Italy. PA in the 3 months preceding the evaluation was assessed and classified as follows: 0 = never or <1 h/week (sedentary), 1 = 1–3 h/week (active), 2 = 4–6 h/week (very active), 3 = >6 h/week (extremely active). A variety of PA types were included, ranging from casual recreational activities to aerobic and strength training exercises. All women completed validated questionnaires for assessment of sexual function (FSFI and Female Sexual Distress Scale-Revised [FSDS-R]), body image related concerns (Body Uneasiness Test), and psychiatric morbidities, including depression and anxiety (Middlesex Hospital Questionnaire). Detailed relationship and sexual histories were obtained. In addition, sexual desire and arousal were specifically evaluated with single questions asking about these domains. The participants were thus classified as having hypoactive sexual desire disorder (HSDD) and/or Female Genital Arousal Disorder (FGAD) based on their responses. All the participants had a physical examination and a clitoral artery doppler ultrasound with measurement of vascular resistance (pulsatility index).
Women engaging in PA had higher total FSFI scores (p = 0.007), a lower risk of having a pathological FSFI score defined as a total score <26.55 (p = 0.017), and lower sexual distress (lower FSDS-R scores, p = 0.017), indicating better overall sexual function. Compared to sedentary women, physically active women scored significantly higher in the desire (p = 0.001), arousal (p = 0.001), lubrication (p = 0.010), and satisfaction (p = 0.010) domains of the FSFI. The frequency of HSDD and FGAD was also lower in women engaging in PA (p = 0.001 and 0.049, respectively).
The relationship between PA and sexual function persisted in multivariable analyses adjusting for age, body mass index (BMI), metabolic syndrome, psychological morbidities, partner's sexual dysfunction, and body image related concerns. Physically active women scored significantly higher in multiple FSFI domains, including desire, arousal, and lubrication. They also showed lower sexual distress and lower clitoral artery vascular resistance in comparison to sedentary women. The negative association between PA and HSDD and FGAD was partly mediated by factors such as BMI, psychological morbidities, and body image-related concerns. Finally, extremely active women had worse sexual function compared to the very active women, as reflected by the significantly lower arousal (p = 0.002), lubrication (p = 0.010), satisfaction (p = 0.015), and total FSFI (p = 0.015) scores. These differences persisted after adjusting for age, BMI, and partner sexual dysfunction. Even compared to the sedentary women, the extremely active women reported lower sexual satisfaction (p = 0.045).
What this changes or adds
Despite the limitation of small sample size and self-reported unstandardized PA, the current study highlights several important aspects about the relationship between PA and female sexual function. First, PA is associated with better sexual function across multiple domains, even after adjustment for multiple important determinants of sexual function. Women engaging in PA may have better clitoral vascularization which likely favorably impacts arousal. These findings highlight the importance of counseling women regarding the importance of PA, not only for improving their overall health but also for improving their sexual function. At the same time, extremely active women may have worse sexual function than their sedentary and less active counterparts. Excessive exercise may reflect obsessive-compulsive personality traits and body dissatisfaction, which could adversely impact sexual function in these women. It may therefore be important to screen women with sexual dysfunction for abnormal behaviors, including disordered eating and excessive PA.
Impact of Infertility on Female Sexual Health
Dong M, et al. Impact of infertility duration on female sexual health. Reprod Biol Endocrinol 2021;19:157.
What we know
Sexual dysfunction is prevalent among women experiencing infertility and likely has a multifactorial etiology. 11,12 The factors contributing to sexual dysfunction in women with infertility may include stress, mood disturbances, relationship discord, and adverse effects of fertility treatments, among others. Limited evidence suggests that a longer duration of infertility may be associated with a higher risk for female sexual dysfunction. 13 This study is the largest to date to explore the impact of infertility duration on female sexual function.
Study results
This was a case–control study performed at a university hospital in China involving 715 women diagnosed with infertility who were <45 years of age. Women with medical conditions such as polycystic ovary syndrome, endometriosis, and premature ovarian insufficiency were excluded, as were women with psychiatric conditions or those who were on medications known to adversely impact sexual function, for example, selective serotonin reuptake inhibitors. Women whose partners had severe male infertility or who were diagnosed with sexual dysfunction were also excluded. The FSFI was used to diagnose sexual dysfunction using a cutoff score of ≤23.45 as is the norm for women in China. Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9). Duration of infertility (defined as the time from the couples' first attempt to conceive to entry in the study) was categorized into four groups: ≤2 years; >2 years, but ≤5 years; >5 years, but ≤8 years; and >8 years. Results showed that as duration of infertility increased, incidence of depression by PHQ-9 scores increased, but the total FSFI and domain scores (desire, arousal, lubrication, orgasm, satisfaction, and pain) were not significantly different between the four groups.
A multivariable logistic regression model was used to assess multiple potential contributing factors, including age, BMI, income, education, stress, physical and sexual activity levels, smoking, alcohol intake, and psychological distress. On multivariable analysis, as the duration of infertility increased, the incidence of sexual dysfunction increased. In women with infertility >8 years, the adjusted odds ratio (AOR) for sexual dysfunction was 5.158 (95% confidence interval [CI]: 1.935–13.746, p = 0.001); findings were also significant for the sexual function domains of arousal (AOR = 2.955, 95% CI: 1.194–7.314, p = 0.019), pain (AOR = 3.811, 95% CI: 1.045–13.897, p = 0.043), and lubrication (AOR = 5.077, 95% CI: 1.340–19.244, p = 0.017).
What this changes or adds
As the duration of infertility increases, women are at greater risk for psychological distress and for sexual dysfunction, especially when the duration of infertility exceeds 8 years. Clinicians caring for women with infertility should be aware of these associations and should regularly screen women experiencing infertility for sexual and mental health disorders. Given that psychological well-being is an important and independent determinant of female sexual function, being alert to the potential interaction between psychological distress and sexual function is particularly salient in women with more longer-standing infertility.
Footnotes
Author Disclosure Statement
Ekta Kapoor has no conflicts of interest directly related to the subject of this manuscript. However, over the past 36 months she has had the following conflicts of interest: She has been a consultant for Astellas and Mithra Pharmaceuticals, Scynexis and Womaness. She has received grant support form Mithra Pharmaceuticals. She has received payment for development of educational content from Med Learning Group and Academy of Continued Healthcare Learning. She has received honoraria for CME activity from CogniMed, PriMed and OBG Management.
Funding Information
No Funding was received for this article.