Effects of a single 20 mg dose of letrozole on ovarian function post dominant follicle selection: an exploratory randomized controlled trial

Abstract

BackgroundOur objective was to explore the impact of a single dose of an aromatase inhibitor (letrozole) administered at defined times of the follicular phase or immediately after ovulation on dominant follicle development, luteogenesis and new follicle wave emergence.MethodsA prospective pilot study using a randomized complete block, controlled, open label design was conducted at an academic clinical research center. Forty-five healthy, female volunteers (25.5 ± 0.9 years, BMI 25.0 ± 0.6 kg/m2) who had not taken hormonal contraceptives for a minimum of 2 months were recruited. A 20 mg dose of Letrozole was administered once orally in each of 3 groups when the dominant follicle reached a diameter of 1) 12 mm, 2) 18 mm, 3) the first day following ovulation (post-ovulation), or 4) treatment was withheld (control). Serial ultrasonography and phlebotomy began on day 4 of the menstrual cycle and continued for 1.5 menstrual cycles. Participants recorded menses and daily events in a life events calendar for the duration of the study. Demographic and single point measurements were compared among groups by ANOVA. Changes in hormone concentrations over time were compared among groups by repeated measures ANOVA. Kruskal-Wallis tests were used for non-normally distributed data.ResultsThe dominant follicle in all treatment groups ovulated. There were no differences among experimental groups in peak follicle diameter, follicular growth rate, endometrial thickness at ovulation or inter-ovulatory interval. Plasma concentrations of estradiol dropped, while FSH and LH concentrations rose following treatment in all treatment groups. Plasma FSH and LH concentrations were higher in the 18 mm group compared to the 12 mm and post-ovulation groups (P < 0.02).ConclusionAdministration of a single 20 mg dose of Letrozole at the times of the menstrual cycle we examined did not induce dominant follicle regression or failure of corpus luteum formation. Letrozole-induced suppression of estradiol synthesis by the dominant follicle was not detrimental to follicle growth or ovulation following follicle selection, likely due to increased circulating concentrations of FSH and LH resulting from a lack of estradiol-induced suppression of the hypothalamic-pituitary-ovarian axis.Trials registration numberClinical trials registration number NCT01046578.

Regulation of Ovarian Cancer Prognosis by Immune Cells in the Tumor Microenvironment

“…These vesicles are released by tumor cells and most other cells types of the TME [ 159 , 160 ]. They mediate the transfer of proteins, lipids, and nucleic acids such as DNAs, mRNAs, and miRNAs between tumor and stroma [ 161 ].…”

“…EVs range from 30 to 150 nm, whereas microvesicular bodies (MVBs) are 100 nm to 1 µm [ 162 ]. EVs carry molecules such as CD24, and epithelial cell adhesion molecule (EPCAM1), which directly regulate cancer-cell migration, proteases (MMP2, MMP9), which promote ECM degradation and cancer invasiveness [ 160 , 163 , 164 ], or EV-associated mRNAs, such as miR21, which may induce resistance to paclitaxel [ 163 , 165 , 166 ].…”

A Retrospective Study of Letrozole Treatment Prior to Human Chorionic Gonadotropin in Women with Polycystic Ovary Syndrome Undergoing In Vitro Fertilization at Risk of Ovarian Hyperstimulation Syndrome

“…Allaway et al found that a single dose of 20 mg of letrozole could lower the E 2 levels while increasing the levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) level when the diameter of dominant ovarian follicles reached 12 mm or 18 mm after ovulation [ 21 ]. However, the changing levels of hormones did not result in the disappearance of dominant follicles, and in this study, the use of letrozole at E 2 peak levels could quickly lower E 2 levels to effectively prevent OHSS [ 21 ]. However, the development of the dominant ovarian follicle was not be affected and the lowered E 2 level was beneficial for embryo transfer [ 21 ].…”

“…However, the changing levels of hormones did not result in the disappearance of dominant follicles, and in this study, the use of letrozole at E 2 peak levels could quickly lower E 2 levels to effectively prevent OHSS [ 21 ]. However, the development of the dominant ovarian follicle was not be affected and the lowered E 2 level was beneficial for embryo transfer [ 21 ]. Another study also indicated that the co-administration of letrozole and gonadotropin in the IVF cycle could increase the expression of integrin in the endometrium and increased endometrial receptivity [ 22 ].…”

Depression, Sexual dysfunction and Quality of Life Among Breast Cancer Patients with Ovarian Function Suppression: A Cross Sectional Study between Ovarian Ablation Verse GnRH Agonists

“…A questionnaire to survey was performed in breast cancer patients younger than 35 years and 8% of patients rejected to receive chemotherapy because of worried about reducing their fertility [14]. GnRHa can protect ovarian function during chemotherapy for HR-negative breast cancer patients [15]. More important for clinicians and patients were to understand the state of ovarian function and protect their ovarian function.…”