Excerpts from the World Medical Literature: Gynaecology

Agrawal P, Singh SM, Able C, et al. Safety of vaginal estrogen therapy for genitourinary syndrome of menopause in women with a history of breast cancer. Obstet Gynecol 2023;142:660–8. Summary: This was an analysis of a US health research network from January 2009 to June 2022, involving patients diagnosed with breast cancer 3 months to 5 years before an initial diagnosis of genitourinary syndrome of menopause (GSM). Breast cancer and GSM diagnoses were from International Classification of Diseases (ICD) codes. Two groups were compared: a study cohort that had at least 3 prescriptions for vaginal estrogen (either estradiol or conjugated estrogens) with at least one prescription 2.7 pg/mL for the estrogen and placebo groups (2.7 pg/mL being a potential cut-off denoting increased risk of breast cancer). No differences in estrone and sex hormone-binding globulin (SHBG) were observed. Comment: The authors concluded, based on this study and previous research, that any changes in serum levels after vaginal estrogen "likely have limited clinical significance". As estradiol is associated with alterations in estrone and SHBG, but these factors were not increased in the study, the authors stated that the increase in serum estradiol in this study was unlikely to have significant physiologic impacts. Together with the observational data above, this study provides additional reassurance about the use of vaginal estrogen to treat GSM in the context of prior breast cancer. That being said, this would still be a decision between each patient and their clinician. For some, the finding of some elevation in serum estrogen (even if not considered clinically significant) may not be acceptable. For others, including perhaps those with severe GSM signs/symptoms, these serum estrogen data may make them more comfortable proceeding with vaginal estrogen. Li FG, Fuchs T, Deans R, et al. Vaginal epithelial histology before and after fractional CO2 laser in postmenopausal women: a double-blind, sham-controlled randomized trial. Am J Obstet Gynecol 2023;229:278.e1–9. Summary: This paper was a histological study within a single-center, double-blind, sham-controlled RCT. The cohort consisted of 49 subjects (46 analyzed) who were postmenopausal and had at least one symptom of GSM for which they had sought medical help and not previously had an energy-based treatment, and where medical therapies had been previously trialled, declined, or otherwise contraindicated. Any previous vaginal estrogen use had to stop 6 months before the start of the trial. Exclusion criteria were active genital infection. Subjects were randomized to laser treatment or sham. For the CO2 laser, 3 vaginal fractional micro-ablative treatments were done 4–8 weeks apart (MonaLisa Touch), at what was described as standard settings. For the sham, minimal energy settings were used with no tissue effect. Primary outcome was vaginal wall biopsies that were taken before and after treatment, and that were pathologically classified into well-estrogenized, poorly estrogenized, or combination. These biopsies were 3 cm above the hymenal ring at the right lateral vaginal wall at baseline and left lateral vaginal wall after 6 months of the laser or sham treatment. Pathologists were specialist gynaecologic pathologists who were blinded. The classification was based on glycogen-rich squamous epithelium, vascularization of the sub-epithelial stroma, and thickness of the basal epithelium, and was found to be reproducible. Subjects were classified according to whether the classification had progressed (worsened), unchanged, or regressed (improved). Other outcomes were subjective symptoms on a visual analogue scale, the Vulvovaginal Symptom Questionnaire, and Vaginal Health Index. The authors found no differences in the pathologic assessment of the vaginal mucosa between laser treatment and the sham. Subgroup analyses showed the same finding. Interestingly, the pathologic classification did not show a strong association with patient symptoms of GSM. Comment: The authors concluded that "fractional CO2 laser is not significantly different from sham treatment and should not be recommended for clinical use for postmenopausal vaginal symptoms". They summarized the literature and remarked that it was contradictory, with some studies showing similar findings to this trial, and others seemingly showing benefits to energy-based therapies. They commented that the latter studies tended to be of small sample size and with non-blinding of pathologists. This histological study is in line with the lack of differences in patient or clinician-reported outcomes after 12 months that were previously reported by the authors for the laser versus sham.1Li F.G. Maheux-Lacroix S. Deans R. et al.Effect of fractional carbon dioxide laser vs sham treatment on symptom severity in women with postmenopausal vaginal symptoms: a randomized clinical trial.JAMA. 2021; 326: 1381-1389Google Scholar Together, these results do not provide evidence for the use of vaginal fractional CO2 laser as a non-hormonal treatment for GSM, which would be of particular interest to patients with a history of breast cancer. It should be noted that there are variations in energy-based treatments, and the results of this trial should not necessarily be extrapolated to these other options. However, the randomized trial evidence from this group would seemingly reduce enthusiasm for this overall treatment approach to GSM. Fortunately, the vaginal estrogen data summarized above would suggest that it remains a feasible treatment for the majority of patients with GSM, including some who have a history of breast cancer. Extraits de la littérature médicale mondiale : gynécologieJournal of Obstetrics and Gynaecology Canada Vol. 46Issue 4PreviewAgrawal P, Singh SM, Able C, et al. Safety of vaginal estrogen therapy for genitourinary syndrome of menopause in women with a history of breast cancer. Obstet Gynecol 2023;142:660–8. Full-Text PDF