Evaluation of efficacy and effect of topical low-dose testosterone (3 mg/mL) on estradiol levels by mass spectrometry in breast cancer patients receiving ovarian suppression and aromatase inhibitor therapy

Author:

Taranto Patrícia1,Sales Diogo de Brito1,Maluf Fernando Cotait1,Guendelmann Rafael Aliosha Kaliks1,Pompei Luciano de Melo2,Leal Alessandro3,Buzaid Antonio Carlos4,Schvartsman Gustavo1

Affiliation:

1. Hospital Israelita Albert Einstein

2. Faculdade de Medicina do ABC

3. NYU Langone Health

4. Beneficência Portuguesa de São Paulo

Abstract

Abstract

Background Premenopausal, high-risk, hormone receptor-positive breast cancer patients are often treated with ovarian suppression in combination with aromatase inhibitors. This combination has important adverse effects, particularly in sexual function, such as vaginal dryness and loss of libido. There is no effective therapy for reduced sexual function in this setting. Our study aimed to determine the efficacy and safety, particularly regarding sexual function, of a low-dose, topical testosterone gel administration.Methods This is a pilot, single-center study, designed to evaluate the efficacy of topical testosterone gel (3 mg/day) in improving sexual function in 29 premenopausal patients on ovarian suppression in combination with an aromatase inhibitor. The primary safety endpoint was to determine serum estradiol, measured by liquid chromatography-mass spectrometry monthly for three consecutive months. The primary efficacy endpoint was assessed by means of the Female Sexual Function Index questionnaire, which include various domains of sexual function such as libido, sexual satisfaction and vaginal lubrication.Results We report the results on 29 patients. Twenty-two patients (75%) completed the 3-month treatment, and seven discontinued treatment. One was excluded after the first visit because she was postmenopausal, one had a mild skin reaction and five discontinued treatment over the three months mainly due to logistical difficulties related to the COVID-19 pandemic. A total of 29 patients maintained the value of baseline mass spectrometry assay for estradiol of less than 2.7 pg/mL during the 3-month treatment in all three measurements. We observed a significant improvement in Female Sexual Function Index measures over the visits, with an increase from a mean of 11.7 at baseline to 19.1 in the third month (p < 0.001), with the greatest improvement observed between the second and third months. Regarding the domains of the questionnaire evaluated separately, desire, excitement, lubrication, orgasm and satisfaction all showed significant improvement over three months of the protocol.Conclusions Our findings suggest that topical testosterone seems to be safe and may be effective in improving sexual function in patients on ovarian suppression and AI. A randomized phase 2 study is warranted.Trial registration The project was submitted and approved through the hospital's SGPP platform in 11/26/2019 (Project No. SGPP: 3938-19) and CAAE (Research Ethics Committee) (CAAE No: 25609719.5.0000.007)

Publisher

Research Square Platform LLC

Reference20 articles.

1. Breast cancer treatment: a review;Waks AG;JAMA,2019

2. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer;Pagani O;N Engl J Med,2014

3. Gray R, Francis BR, Regan P. M, Effects of ovarian or suppression on breast cancer recurrence and survival: patient-level meta-analyses of 14,999 pre-menopausal woman in 25 randomized trials. 2023 ASCO Annual Meeting. Oral Abstract Session.

4. Quality of life of postmenopausal women in the arimidex, tamoxifen, alone or in combination (ATAC) adjuvant breast cancer trial;Fallowfield L;J Clin Oncol,2004

5. Ovarian suppression for adjuvant treatment of hormone receptor-positive early breast cancer;Bui KT;Cochrane Database Syst Rev,2020

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