Table 2.

RCTs assessing the safety of vaginal and oral selective estrogen receptor modulator therapies for treatment of genitourinary syndrome of menopause in breast cancer survivors.

Author and year	Total number of breast cancer survivors as study participants	Intervention regimen (n)	Comparator regimen (n)	Patient Characteristics	Assessment points	Serum estrogen levels	Recurrence of breast cancer
Melisko et al, 2016 30	76	Estring 2 mg silicone ring, inserted once a day for 90 days (n = 40)	0.5 g 1% intravaginal testosterone (IVT), 0.5 g a day for 2 weeks, 3 times a week from weeks 3 to 10 (n = 36)	Treated with an aromatase inhibitor for at least 30 days	Assessed at baseline, 4 and 12 weeks	Mean values	No recurrence noted
						Estring ring at baseline 26.8 pg/mL
						IVT at baseline 9.0 pg/mL
						A transient elevation in estradiol was observed in 12% of patients’ using IVT (range, 11–113 pg/mL. Persistent elevation in estradiol observed in and additional 12% of patients' using IVT (range, 16–45 pg/mL)
						A transient elevation in estradiol was observed in 11% of patients’ using the Estring ring (range, 11–29 pg/mL). No persistent elevation in estradiol was seen in any patients' using the Estring vaginal ring
Barton et al, 2018 28	440	i) DHEA 3.25 mg/d moisturiser gel of 12 weeks (n = 147). ii)DHEA 6.5 mg/d moisturiser gel for 12 weeks (n = 149)	Control plain moisturiser, 1 syringe of gel daily every night for 12 weeks (n = 147)	If patients on endocrine therapy (tamoxifen or aromatase inhibitors), they must have been receiving the treatment for 2 months prior to the start of the trial without planned changes	Assessed at baseline and at 12 weeks following daily application	Change in mean concentration of estradiol from baseline levels	No recurrence noted
						Plain moisturiser – 0.2 ± 2.5 pg/mL, 3.25 mcg/dL DHEA 0.9 ± 5.0, 6.5 mcg/dL DHEA - 0.6 ± 1.9
						Serum estradiol was significantly increased from baseline at 12 weeks in those on 6.5 mg/day DHEA but not those on 3.25 mg/day and not in those on aromatase inhibitors
Hirschberg et al, 2020 29	61	0.005% (50 ug/g) Estriol vaginal gel, 1 g a day for 3 weeks, 2 g a week during weeks 4–12 (n = 50)	Non-hormonal moisturising gel, 1 g a day for 3 weeks, 2 g a week during weeks 4–12 (n = 11)	Hormone receptor positive and any HER2 status, treated with an aromatase inhibitor for at least 6 months	Assessed 2 weeks prior to the start of treatment, at baseline and at weeks 1, 3, 8 and 12 of treatment and 30 +/− 5 days after the last dose	Median estriol levels	No recurrence noted
						Estriol gel at baseline 0.5 pg/mL, week 1 3.9 pg/mL, week 3 1.9 pg/mL, week 8 0.5 pg/mL and week 12 0.5 pg/mL
						Moisturising gel at baseline 0.5 pg/mL, week 1 0.5 pg/mL, week 3 0.5 pg/mL, week 8 0.5 pg/mL and week 12 0.5 pg/mL
						Estriol levels increased initially and normalised by week 12, and estradiol and estrone remained mostly undetectable throughout the study