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Chemopreventive Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
A study published in the journal Cell Chemical Biology has suggested that patients taking a combination of palbociclib (IbranceTM) and letrozole (FemaraTM) (see Chapters 6 and 8, respectively), a popular drug combination for treating breast cancer, should avoid foods rich in xenoestrogens (i.e., estrogen-mimicking compounds). Palbociclib was developed by Pfizer for the treatment of ER-positive/HER2-negative breast cancer, and is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Letrozole is an aromatase inhibitor used in the treatment of hormonally responsive breast cancer after surgery. The research showed that two common dietary xenoestrogens, genistein (Figure 12.14) and zearalenone (Figure 12.19), which are found in many different plant-based foods, appear to potently reverse the effects of palbociclib/letrozole in tumor cells growing in vitro. Structure of zearalenone.
Minimizing Blood Loss
Published in John C. Petrozza, Uterine Fibroids, 2020
Elise Bardawil, Jessica B. Spencer
Letrozole is an aromatase inhibitor that blocks estrogen synthesis. It has been used to decrease the size of myomas, and thus potentially decrease intraoperative blood loss. One prospective, randomized study looking at laparoscopic myomectomy gave 40 patients 3 months of daily oral letrozole and norethindrone acetate and compared outcomes with patients who were not pretreated. The authors found a significant decrease in intraoperative blood loss in the pretreated arm, with a mean of 271 mL. However, they reported that the tissue plane between the myoma capsule and surrounding myometrium was better defined in the arm that was not pretreated [22]. In this, letrozole is similar to a GnRH agonist. This potential increased intraoperative difficulty must be weighed against the decreased intraoperative blood loss when considering this method of treatment.
Statistical Monitoring of Safety and Efficacy
Published in Susan Halabi, Stefan Michiels, Textbook of Clinical Trials in Oncology, 2019
Second, there may not be sufficient safety data collected at the time of interim analysis to allow termination of the trial. Regulators might want the trial to continue at least in the experimental group in order to be sure an adequate safety profile has been attained. Indeed, early termination does not always answer the efficacy question originally posed. In the National Cancer Institute of Canada MA-17 early-stage breast cancer trial evaluating letrozole in postmenopausal women after five years of tamoxifen therapy, patients were randomized to five years of letrozole or placebo [37]. The trial was terminated by the DMC with median follow-up of 2.4 years when a letrozole-to-placebo DFS hazard ratio of 0.43 was observed with p = 0.00008. In addition to the problem of extreme value, the trial did not answer the question regarding the efficacy of five-year letrozole therapy—a question of considerable interest to practicing oncologists. In a somewhat similar situation, the DMC for the cardiovascular and cancer prevention trial of estrogen plus progestin of the Women's Health Initiative had observed data for elevated incidence of breast cancer in the hormone group but felt that these early results were not persuasive enough to change practice, so they delayed their termination decision until more data arrived [38].
Comparative study of DHEA and letrozole induced polycystic ovary syndrome in post-pubertal rats
Published in Gynecological Endocrinology, 2022
DHEA subcutaneous injection and letrozole instillation are the most commonly reported induction methods of PCOS in rats [5]. Theoretical basis of DHEA modeling: the modeling principle of this method is that some PCOS patients show symptoms in adolescence, and the levels of serum DHEA and DHEAS increase. It is speculated that the increase of DHEA may be an important cause of PCOS. Δ5 pathway is transformed into the intermediate product of androstenedione, which can increase the level of androstenedione through exogenous pathway, and then increase the level of testosterone, resulting in the pathological characteristics of PCOS [6]. The theoretical basis of letrozole modeling: the high androgen environment in local ovary and blood circulation is the key to PCOS. Aromatase is the last step of the rate-limiting enzyme in the transformation of androgen to estrogen. The decreased activity of this enzyme in the ovary can lead to the increase of androgen level and progress to polycystic ovary. It is widely found in various tissues of the human body, such as ovary, placenta, testis, peripheral adipose tissue, etc. As an aromatase inhibitor, letrozole can prevent the production of estrogen, leading to a high androgen environment in the body [7]. These two modeling methods are the most commonly used and classic modeling methods in current literature reports, so we choose these two models for comparative study.
Stimulated cycle versus artificial cycle for frozen embryo transfer in patients with polycystic ovary syndrome: a Meta-analysis
Published in Gynecological Endocrinology, 2021
Mei Fang Zeng, Xin Zhou, Jin Liang Duan
With regard to the methods for endometrial preparation in FET cycles, there are three main categories of embryo transfer protocols: natural cycle (NC), artificial cycle (AC) and mild ovarian stimulation cycle. The NC has its timing of FET based on patients’ own natural ovulation cycle [6] and the AC has estrogen and progesterone administered to modulate the patients’ body cycle and adjust the endometrium to be receptive for embryos [7]. The most commonly used FET protocol for PCOS patients is the AC. The main advantage of AC-FET is that it is easy to plan, thus improving patient convenience. However, several studies have reported a higher live birth rate (LBR) with the stimulation cycle rather than the AC for FET [8]. In the mild ovarian stimulation cycle, ovulation drugs include clomiphene, letrozole and human menopausal gonadotrophin (HMG). However, clomiphene is a selective estrogen receptor modulator that reduces endometrial thickness [9]. Letrozole is an aromatase inhibitor that does not decrease estrogen receptors and does not negatively affect endometrial thickness [10]. Letrozole has been widely used as a potential ovulation stimulator for PCOS women with mono-ovulation and to decrease OHSS [11]. HMG may also be an alternative follicle-stimulating medication for endometrial preparation. However, HMG may stimulate multiple follicle growth and increase the chance of OHSS, thus increasing the cycle cancelation rate [12]. For PCOS patients, both the AC and mild ovarian stimulation cycle can be selected. The choice of the best endometrial preparation protocol adapted to PCOS patients is still a matter of debate.
Alteration at transcriptional level of cardiac renin–angiotensin system by letrozole treatment
Published in Acta Cardiologica, 2019
Shahnaz Shekarforoush, Farhad Koohpeyma, Fatemeh Safari
Kumru et al demonstrated that serum oestradiol levels were reduced significantly by the administration of both doses of letrozole (1 and 2 mg/kg) [12]. Given the effects of sex hormones on the RAS, it is likely that the reported side effects of letrozole on the cardiovascular system are related to its hypoestrogenic property. Previous studies have shown that the surgical loss of ovarian oestrogens is associated with development of hypertension, cardiac hypertrophy, and oxidative stress [29]. In fact, oestrogen deficiency leads to increased tissue expression of ACE and AT1 receptor and decreased tissue expression of AT2 receptor [30,31], whereas testosterone upregulates the classical RAS [32]. In addition, oestrogen levels are positively associated with HDL-C levels and AIs can interrupt this interplay thus increasing the odds of a developing cardiovascular disease [33].