High doses of pelvic RT cause tissue injury as inflammation and fibrosis who leads to problems in vaginal function such as dryness, shortening and tightening of the vagina which could cause discomfort and affect sexual enjoyment and patient’s overall wellbeing. In this longitudinal prospective study, the association between pelvic RT and sexual function was studied in both patients with primary cervical cancer and in patients with primary uterine tumors.

At first, the relationship between sexual activity and different types of RT treatments was studied in the primary cervical cancer patients. Here, we showed that the sexual activity was significantly higher in patients with pelvic RT alone compared to patients with pelvic RT + cervical brachytherapy/boost. The relationship between pelvic RT and side effects as sexual problems has been studied by Kirchheiner et al. (2022). However, in this study, all patients received additional brachytherapy (100%) and no comparisons between RT alone and RT + brachytherapy were therefore performed [11]. As far as we know, this is the first prospective study that shows a significant relationship between sexual activity and type of pelvic RT treatment in primary cervical cancer patients. This difference in sexual activity between the cervical cancer patients with RT + brachytherapy vs. RT alone could partly be attributed to increased development of fibrosis in the vagina because of a higher dose of radiation when the patients are treated with RT + brachytherapy/boost compared to RT alone. The high doses of brachytherapy/boost in addition to RT could also damage the vaginal epithelium and reduce the number of estrogen receptors which further reduces the ability for vaginal lubrication [7]. We suggest that additional cervical brachytherapy/boost has a negative impact on sexual activity in primary cervical cancer patients. Additional brachytherapy/boost gives a higher total radiation dose which increases the risk of developing fibrosis/atrophy of the vaginal epithelium which leads to tightening and dryness of the vagina with further impaired sexual function. However, a larger randomized study is needed to further elucidate this issue.

We further studied the sexual activity in primary uterine tumor patients in relation to type of RT by using the EORTC-QLQ-EN24 form. We found no significant relationship in sexual activity between primary uterine tumor patients with pelvic RT alone and pelvic RT and additional vaginal brachytherapy/boost. Similar findings were reported by Karabuga et al. (2015) who studied 144 primary endometrial cancer patients by using the quality-of-life questionnaire EORTC-QLQ-CX24 [9]. A large, randomized study of primary endometrial cancer patients did not make the comparison between patients with pelvic RT alone and patients with pelvic RT + vaginal brachytherapy/boost in relation to sexual symptoms [12].

There is thus a discrepancy between cervical cancer patients and the patients with primary uterine tumors with regards to the effect of RT on sexual activity. One explanation could be thatthe cervical cancer patients receive a much higher total radiation dose compared to the uterine tumor patients, increasing the risk of development of fibrosis in the vagina. Since, most cervical cancer patients and very few uterine tumor patients are premenopausal, the RT induced reduction in the estrogen production in premenopausal women (which further leads to reduced stimulation/lubrication of the vaginal epithelium) could also in part account for this discrepancy.

Further, we studied the sexual activity in primary cervical cancer who had received curative RT. Here, we showed that the sexual activity increased from RT start to 12 months after RT. Even though the sexual activity increased from RT start to 12 months after RT the frequency of sexual activity was still low (52.5%) 12 months after RT, which is similar results found by others [11]. Studies on an age-matched norm population reported that the sexual activity was 72% which is a high frequency compared to the cervical cancer patients with RT [7]. Since these patients are women in mid-life with a mean age around 50 years, we suggest that the frequency of sexual activity in primary cervical cancer patients is affected by RT and is still at a low level 12 months after RT.

Further, we studied the sexual behavior and perception in cervical cancer patients with RT who were sexually active. Most patients (81.8%) felt that their vagina was dry, 60% felt that their vagina was short, 50% had pain during intercourse and 30% experienced tightening of their vagina 12 months after RT. Similar findings have been reported by others, but with a higher frequency of tightening of the vagina (50% compared to 30% in our study) [11]. Additional cervical brachytherapy was given to all patients (100%) in the previous study compared to only 83.7% in our study. The resulting increased fibrosis could account for the increased tightening of the vagina in the previous study.

At 3 months after RT, 73.7% of the cervical cancer patients worried that sex would be painful. A high frequency of patients 63.4% still felt dissatisfied with their body at 12 months after RT, showing that treatment with high doses of pelvic RT for these patients also affects the psychological aspects of the sexuality with a high frequency of patients experiencing changes in their body image.

The relationship between pelvic RT and sexual function was also studied in patients with primary uterine tumors. Here we showed that the sexual interest increased, and the sexual activity tended to increase 12 months after RT compared to at RT start. However, the frequency of sexual interest and the sexual activity was still at a low level of 40.7% and 42.3% 12 months after RT. These results are in line with a study on endometrial cancer patients with pelvic RT or brachytherapy, where the sexual activity and sexual interest was 39% 12 months after RT [10]. The sexual activity in our study and the previous study was significantly reduced compared to the age-matched norm population for both the Pelvic RT and brachytherapy/boost group [10]. We can thus conclude that although the sexual interest and sexual activity in primary uterine tumors seemed to increase from RT start to 12 months after RT, they remain at a low level 12 months after RT.

Very few matched cases were present in the group of primary uterine tumor patients that were sexually active. Out of these patients, 50% felt that their vagina was dry, 50% reported pain during sexual intercourse and 60% felt that their vagina was too short/tight. In previous reports no detailed information regarding these specific sexual symptoms was presented [4, 12]. However, it is difficult to draw valid conclusions out of our results since there were very few patients with primary uterine tumors who were sexually active and larger prospective studies are recommended to confirm our initial findings.

Next, the use of systemic and local estrogen treatment in relation to sexual activity was studied in primary cervical cancer and uterine tumor patients with RT. Our findings show that treatment of primary cervical cancer patients with systemic estrogens significantly improved the sexual activity before RT, at 3 months and 12 months after RT compared to patients without systemic estrogen treatment [11]. At RT start, cervical cancer patients with local estrogen treatment tended to have an increased sexual activity compared to patients without local estrogen treatment but this increase was not statistically significant. No significant difference was seen either at 3 or 12 months after RT, suggesting that the dose of local estrogen applicated was not sufficient to improve the sexual activity in cervical cancer patients with RT. It was shown in a previous study, that RT reduced the number of estrogen receptors in the vaginal epithelium in cervical cancer patients [17], suggesting that the cervical cancer patients with RT probably need a higher dose of local estrogen in order to get a sufficient stimulation/lubrication of the vaginal epithelium which could lead to improved sexual activity. In the primary uterine patients with RT, there were no significant differences in sexual activity between patients with or without systemic (few cases) or local estrogen treatment. It could be speculated that a higher dose of local estrogens could be of benefit for primary uterine tumor patients with RT. However, further preclinical, and larger randomized clinical studies are needed to clarify this issue.

Taken together, our study suggests cervical cancer patients and primary uterine tumor patients require early medical interventions and attention from the health care. Future care should include treatment with both systemic and local estrogens, local lubricants, usage of vaginal dilatators and sexual advice by curator. Such interventions are even more important for the cervical cancer patients who receive additional cervical brachytherapy/boost.

The strength of this study is that it is prospective and longitudinal, and all patients received the same type of RT treatments with IMRT technique. However, the small sample size, especially in the primary uterine tumor group is a limiting factor.

In conclusion, the sexual activity was significantly higher in primary cervical cancer patients with pelvic RT alone compared to patients with pelvic RT and additional cervical brachytherapy/boost, suggesting that additional cervical brachytherapy/boost has a negative impact on sexual activity in primary cervical cancer patients. No such relationship was seen in the primary uterine tumors. Very few of the cervical cancer patients 52.5%, and 43.2% of the uterine tumor patients were sexually active 12 months after RT. Treatment of primary cervical cancer patients with systemic estrogens significantly improved the sexual activity before RT, at 3 months and 12 months after RT compared to patients without systemic estrogen treatment. However, treatment with local estrogens did not improve the sexual activity in the cervical cancer or in uterine tumor patients after RT. Future care should include use of systemic and local estrogens, local lubricants, vaginal dilatators, and sexual advice by curator, especially for the cervical cancer patients who receive brachytherapy/boost.