• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6055-6059
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• 2015

Background: Medication policy development in Thailand is continually promoting rational drug use. Letrozole, an endocrine therapy drug, is usually prescribed for post-menopausal status early and advanced stage breast cancer. After Ministry of Public Health announced Letrozole as compulsory licensed drug in 2009, more breast cancer patients can access to this drug at low cost especially those within universal coverage schemes. To ensure that Letrozole is rationally prescribed, the drug utilization study was conducted. Objectives: The aim of this study was to describe the appropriate use of Letrozole in breast cancer and the relationship between appropriate use and health benefit schemes. Materials and Methods: A retrospective study to evaluate use of Letrozole in breast cancer patients was performed for six months between January - June 2010 in seven regional cancer hospitals, Thailand. All prescriptions of Letrozole were identified from pharmacy dispensing databases and prescription papers. A medical record review was also performed to evaluate appropriate use referring to the drug use evaluation criteria. The approved criterion of this study was referred from the guideline of Thai National Formulary version 2010. Results: There were 681 prescriptions of Letrozole for 254 breast cancer patients with an average age of $58.6{\pm}10.0years$. The patients in universal coverage scheme (UCS), civil servant medication benefit scheme (CSMBS) and social security scheme (SSS) were 77.7%, 18.5% and 8.7% respectively. 10.6% were prescribed Letrozole for the first time. Letrozole were prescribed by oncologists (82.8%). The average number of tablets per prescription was $58{\pm}10$. Calcium supplements were prescribed concomitant with Letrozole for 19.4%. To assess drug use evaluation criteria, 45 prescriptions were excluded because of uncompleted clinical data, 636 prescriptions were evaluated. The study showed 86 prescriptions (13.5%) with inappropriate use including 6 (0.9%) not prescribed for estrogen receptor (ER) and/or progesterone receptor (PR) positive, 31 (4.9%) not prescribed for post-menopausal and 49 (7.7%) not prescribed for an appropriate duration. Appropriate use percentages in different health benefit schemes were similar, 85.7% of CSMBS, 86.4% of SSS and 86.7% of UCS. The relationship between health benefit scheme and appropriate use of Letrozole was not significantly different, ${\chi}^2$ (2, N = 636) = 0.081, p > 0.05. Conclusions: The study showed inappropriate use in breast cancer patients because of non-compliance with duration, menopausal status and hormone receptor requirements. To prescribe appropriate indication did not referred to the appropriate practice along the treatment. Drug use evaluation proved very useful for detecting the sign of inappropriate use and allows immediate feedback to the stakeholder for developing medication policy in the future. Importantly, there was no significantly difference in appropriate use of Letrozole across health benefit schemes.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.3
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• pp.115-121
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• 2013

Objective: Letrozole and estradiol valerate are used to treat some hormonally-responsive symptoms and also in modeling of the polycystic ovary syndrome. However, the stereological analysis of the ovary has received less attention. Estimation of the whole ovary volume using the Cavalieri method can be applied in any orientation desired, but estimation of the mean volume of the oocytes requires isotropic uniform random sectioning. Here, a combined method was developed for estimating the parameters. To our knowledge, no comparison has been made of the effects of letrozole and estradiol on the ovary. Methods: Sixty rats were divided into 4 groups receiving estradiol (4 mg/kg), olive oil, letrozole (1 mg/kg), or normal saline. After 21 days, their ovaries were studied. Results: Relative to the control group, the total volume of the ovary and the cortex increased in the letrozole-treated and estradiol-treated rats. In addition, the number of the preantral, antral, and granulosa cells decreased by 43% to 56% in the letrozole- and estradiol-treated rats. On average, a 19% increase was observed in the atretic oocytes of the letrozole-treated and estradiol-treated rats, but the mean oocyte volume decreased by 29% to 44% in letrozole- and estradiol-treated rats. Furthermore, the letrozole-treated rats showed a 5-fold and 7-fold increase in the volume of the cysts and corpus luteum, respectively. A 3-fold increase was found in the volume of both the cysts and corpus luteum in the estradiol group. Conclusion: The structural changes of the ovary were most pronounced in the letrozole-treated animals.

• Korean Chemical Engineering Research
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• v.59 no.4
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• pp.493-502
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• 2021

We prepared and investigated a biosynthesized nanoparticulate system with high adsorption and release capacity of letrozole. Silver nanoparticles (AgNPs) were biosynthesized using olive leaf extract. Cysteine was capped AgNPs to increase the adsorption capacity and suitable interaction between nanoparticles and drug. Morphology and size of nanoparticles were confirmed using transmission electron microscopy (TEM). Nanoparticles were spherical with an average diameter of less than 100 nm. Cysteine capping was successfully confirmed by Fourier transform infrared resonance (FTIR) spectroscopy and elemental analysis (CHN). Also, the factors of letrozole adsorption were optimized and the linear and non-linear forms of isotherms and kinetics were studied. Confirmation of the adsorption data of letrozole by cysteine capped nanoparticles in the Langmuir isotherm model indicated the homogeneous binding site of modified nanoparticles surface. Furthermore, the adsorption rate was kinetically adjusted to the pseudo-second-order model, and a high adsorption rate was observed, indicating that cysteine coated nanoparticles are a promising adsorbent for letrozole delivery. Finally, the kinetic release profile of letrozole loaded modified nanoparticles in simulated gastric and intestinal buffers was studied. Nearly 40% of letrozole was released in simulated gastric fluid with pH 1.2, in 30 min and the rest of it (60%) was released in simulated intestinal fluid with pH 7.4 in 10 h. These results indicate the efficiency of the cysteine capped AgNPs for adsorption and release of drug letrozole for breast cancer therapy.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.2
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• pp.143-153
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• 2008

Objective: To investigate the effects of aromatase inhibitor on reproductive hormone profiles and evaluate it's ovulation inducing capability in anovulatory infertile women. Methods: We quantified the blood levels of reproductive hormones from 30 healthy normal cycling women in natural cycle (control) and letrozole medicated cycle (study). LH, FSH, estradiol, testosterone, DHEA-S were quantified on third, 11th, 21th day in both cycles, and on 21th day, progesterone was added. Sixth anovulatory infertile women received either letrozole or clomiphene citrate for ovulation induction (n=30 in each groups). We compared the clinical parameters such as ovulation rate, pregnancy rate, the day of LH surge, number of follicles and endometrial thickness, cervical mucus amount, spinnbarkeit, mean diameter of follicles on the day of LH surge. Results: Letrozole had no effect on the LH, FSH, estradiol, DHEA-S secretion but there were significant increase in testosterone level on day 11 and progesterone level on day 21 in letrozole medicated cycle compared than control cycle ($0.40{\pm}0.16$ vs $0.28{\pm}0.11\;ng/ml$, p=0.002, $18.18{\pm}13.07$ vs $8.38{\pm}7.64\;ng/ml$, p=0.001, respectively). In comparison between letrozole and clomiphene groups, there were no significant difference in ovulation rate, pregnancy rate, number of mature follicle, mean diameter of follicles, but showed earlier LH surge, thicker endometrium, more cervical mucus, and higher spinnbarkeit in letrozole group ($12.12{\pm}2.46$ vs $14.52{\pm}3.18$ days, p=0.006, $10.48{\pm}1.23$ vs $8.52{\pm}0.93\;mm$, p=0.000, $2.04{\pm}0.61$ vs $1.57{\pm}0.59$, p=0.012, $6.00{\pm}1.12$ vs $4.95{\pm}1.61\;cm$, p=0.003, respectively). Conclusion: Letrozole may augment folliculogenesis and improve the endometrial condition for implantation in normal cycling women. Ovulation efficacy of letrozole in anovulatory women was comparable to clomiphene citrate and letrozole may be more physiological in ovulation induction.

• Animal Bioscience
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• v.35 no.11
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• pp.1666-1674
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• 2022

Objective: Letrozole, a potent aromatase inhibitor, is known to have the potential to modify male reproductive function by altering sex hormone levels. This study aimed to evaluate the semen and testicular characteristics and hormonal profile of aged Mrakhoz bucks (Capra hircus) treated with letrozole. Methods: Twelve Markhoz male goats, aged between 4.5 to 5.5 years with an average body weight (BW) of 61.05±4.97 kg were used for the study. Animals were randomly divided into two equal groups and subcutaneously received either 0.25 mg/kg BW of letrozole or a control every week for 2 months. The semen collections were performed every 10 days, and blood samples and testicular biometric records were collected at 20 days intervals. Results: Letrozole causes increased testosterone and follicle-stimulating hormone levels, testosterone to estradiol ratio, semen index and reaction time during the period from 20th to 60th days (p<0.05). Furthermore, letrozole-treated bucks had higher semen volume, sperm concentration, and total sperm per ejaculate from 30th to 60th days (p<0.05). However, no differences occurred between the groups in scrotal circumference, relative testicular volume, semen pH, abnormality, acrosome integrity, and membrane integrity of sperm during the study (p>0.05). The serum luteinizing hormone levels, sperm viability, motility, and progressive motility increased, and estradiol levels decreased after 40th to 60th days of letrozole treatment (p<0.05). Conclusion: Letrozole application to aged Markhoz bucks provokes reproductive hormonal axis which, in turn, induces enhancement of semen production and quality.

• Journal of Gastric Cancer
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• v.11 no.3
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• pp.180-184
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• 2011

Letrozole is a drug used in the treatment of postmenopausal women with breast and ovarian tumours. There is no evidence in the literature indicating its use in treating gastric cancer. We present a 68 year old lady admitted from the emergency department with weight loss, malaise and anaemia. Investigations confirmed the presence of two different primary tumours in the left breast and the stomach. Following that this patient with oestrogen receptor positive breast cancer and oestrogen receptor negative gastric cancer was treated with letrozole for her breast cancer followed by a gastric resection. Independent histology by two pathologists pre-operatively diagnosed gastric adenocarcinoma. Post-operatively, independent analysis of the resected stomach, omentum and lymph nodes revealed no evidence of gastric cancer. Therefore we conclude that there is a possibility of letrozole having an effect on gastric cancer. Further studies are needed.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.1
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• pp.73-81
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• 2010

Objective: To examine the efficacy of letrozole in infertile women showing a poor endometrial development at previous ovulation induction cycle by using clomiphene citrate. Methods: Eighteen infertile women were selected who showed a poor endometrial development (endometrial thickness$\leq$6.5 mm) after clomiphene treatment (50~100 mg) as ovulation induction for timed coitus. The mean age of the patients was $30.7{\pm}2.8$ years old and the mean duration of infertility was $33.1{\pm}26.6$ months. The infertility factors were identified as corrected endometriosis (n=1), polycystic ovary syndrome (n=5) and unexplained (n=12). Letrozole was given orally in a dose of 2.5 mg for 5 days starting 3~5 of menstrual cycle. Results: The number of follicles was significantly lower in the letrozole cycle when compared with previous clomiphene cycle ($1.1{\pm}0.3$ vs. $2.2{\pm}1.5$, p=0.011). The endometrial thickness (mm) at the time of triggering or LH surge was significantly greater in the letrozole cycle ($8.4{\pm}1.7$ vs. $5.8{\pm}0.5$, p<0.001). The endometrial pattern 'type C' was significantly higher in the letrozole cycle (94.4% vs. 50%, p=0.036). The pregnancy was achieved in 11.1% of the letrozole cycle. Conclusion: Use of letrozole was associated with more thick and improved endometrium than previous clomiphene cycles in which thin endometrium was identified. Use of letrozole appears to be an effective strategy for second-line treatment in women with inadequate endometrial response to clomiphene.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8975-8979
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• 2014

Objective: To explore the possible significance of aromatase P450 in endometrial hyperplasia with a background of polycystic ovary syndrome (PCOS). Methods: Immunohistochemistry was used to determine the expression of aromatase P450 in endometrium of PCOS patients. Semiquantitative analysis of aromatase P450 expression of mRNA and protein level wasalso carried out by real-time quantitative RT-PCR method. After endometrial cells were stimulated by testosterone and letrozole in vitro, the estradiol ($E_2$) level was determined, and the expression of cell aromatase P450 mRNA was assessed. Results: The aromatase P450 mRNA level was increased in endometria of PCOS patients. When endometrial cells were cultured with $10^{-6}M$ testosterone, the $E_2$ level in the culture medium increased. An inhibitory effect on $E_2$ generation and expression of aromatase P450 mRNA was observed when the endometrial cells were treated with $10^{-5}M$ letrozole. Conclusions: There is an increased expression of aromatase P450 in PCOS patient endometrium. Androgen stimulation could enhance the synthesis of aromatase P450 mRNA and the production of $E_2$ in endometrial cells in vitro while letrozole could do the reverse.

• Proceedings of the KAIS Fall Conference
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• 2010.05b
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• pp.1230-1232
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• 2010

A simple, rapid and validated reverse d phase liquid chromatographic method has been developed for the determination of Letrozole (LZ) in pharmaceutical dosage. LZ was separated on ODS analytical column with a mixture of acetonitrile, water in the ratio 50:50 (v/v) as mobile phase at a flow rate of 1.0 mL /min. The effluent was monitored by UV detection at 265nm. Calibration plot was linear in the range of 160 to $240{\mu}g$/mL with the linear regression (r) = 0.999. The method was validated for recovery, precision, specificity.

• Clinical and Experimental Reproductive Medicine
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• v.36 no.2
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• pp.111-119
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• 2009

Objective: The aim of this study was to compare the clinical efficacy of clomiphene citrate (CC) and letrozole combined with gonadotropins for controlled ovarian stimulation (COS) in patients with CC-induced thin endometrium Methods: Fifty-one intrauterine insemination cycles performed in patients who previously had a thin endometrium (<8 mm) to ovulation induction using CC were included in this study. A CC 100 mg/day (CC+gonadotropin group, n=26) or letrozole 2.5 or 5 mg/day (letrozole+gonadotropin group, n=25) was administered on day 3~7 of the menstrual cycle, combined with gonadotropins at dose 75~150 IU every other day starting on day 5~7. We compared total dose of gonadotropin used, endometrial thickness, endometrial pattern, number of follicles ${\geq}14\;mm$ on hCG day, pregnancy rate and multiple pregnancy rate between the two groups, which were statistically analyzed using Mann-Whitney U test or Fisher's exact test, where appropriate. Results: There were no significant differences in clinical characteristics such as age, duration of infertility, number of previous IUI cycles, basal serum hormone levels and cause of infertility between the two groups. In both groups, the endometrium was significantly thicker than that of previous ovulation induction cycles using CC. No significant differences were found in the total dose of gonadotropin used, day of hCG administration, the rate of triple endometrium and pregnancy rate. The number of follicles ${\geq}14\;mm$ was significantly lower ($3.7{\pm}1.7$ vs. $2.8{\pm}1.7$, p=0.03) and the endometrium on hCG day was significantly thicker ($7.7{\pm}1.5$ vs. $9.1{\pm}1.7$, p=0.001) in letrozole+gonadotropin group compared to CC+gonadotropin group. Conclusion: The clomiphene citrate and letrozole combined with gonadotropins appear to avoid the undesirable effects on the endometrium frequently seen with CC for ovulation induction. However, in terms of adequate endometrial development or optimal follicular growth, letrozole may be more beneficial than CC for gonadotropin-combined COS in patients with CC-induced thin endometrium. Further prospective randomized controlled studies in a larger scale will be necessary to confirm our findings.