PCOS: diagnosis and management of related infertility

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. It is characterised by a combination of hyperandrogenism (either clinical or biochemical), chronic oligo/anovulation, and polycystic ovaries. It is frequently associated with insulin resistance and obesity. PCOS receives considerable attention because of its high prevalence and possible reproductive, metabolic, and cardiovascular consequences. It is the most common cause of anovulatory infertility. Ovulation induction with an aromatase inhibitor or anti-oestrogen is the first-line medical treatment. The aim of ovulation induction is monofollicular growth to avoid multiple pregnancy. The second-line treatments include gonadotrophins and laparoscopic ovarian drilling. The role and benefit of metformin in ovulation induction is uncertain. Woman with PCOS undergoing IVF are at significant risk of ovarian hyperstimulation syndrome. Women with PCOS are also at an increased risk of developing gestational diabetes, pregnancy-induced hypertension, and pre-eclampsia.     

Do men with normal testosterone–oestradiol ratios benefit from letrozole for the treatment of male infertility?

Research question

Previous studies of aromatase inhibitors on male infertility have focused on men with low testosterone–oestradiol ratio of less than 10. Can aromatase inhibitors improve spermatogenesis in men with idiopathic male infertility with normal testosterone–oestradiol ratio?

三苯氧胺与来曲唑治疗ER阳性乳腺癌的临床疗效及对血清雌二醇水平和远期预后的影响

目的探讨三苯氧胺与来曲唑治疗雌激素受体(ER)阳性乳腺癌的临床疗效及对血清雌二醇(E2)水平和远期预后的影响。方法采用简单随机抽样法将110例ER阳性乳腺癌患者分为对照组(n=53)和研究组(n=57)。两组患者均接受长春瑞滨联合顺铂治疗,对照组患者在此基础上接受三苯氧胺治疗,研究组患者在此基础上接受来曲唑治疗,随访3年。比较两组患者的临床疗效、血清肿瘤标志物和E2水平、子宫内膜情况、不良反应发生率及生存情况。结果研究组患者的疾病控制率为92.98%,高于对照组的79.25%,差异有统计学意义(P<0.05)。治疗前,两组患者的血清糖类抗原153(CA153)、癌胚抗原(CEA)及E2水平比较,差异均无统计学意义(P>0.05)。治疗后3个月,两组患者的血清CEA和CA153水平均较本组治疗前降低,且研究组患者的血清CEA和CA153水平均低于对照组,差异均有统计学意义(P<0.05)。治疗后3、6、12个月,研究组患者的血清E2水平均低于治疗前,对照组患者的血清E2水平均高于治疗前,差异均有统计学意义(P<0.05)。病理结果提示,治疗后对照组中子宫内膜息肉2例,内膜不典型增生1例。两组患者恶心呕吐、便秘、肝肾功能不全、血小板减少、粒细胞减少及白细胞降低的发生率比较,差异均无统计学意义(P> 0.05)。研究组患者的3年生存情况优于对照组(P<0.05)。结论来曲唑治疗ER阳性乳腺癌的临床疗效优于三苯氧胺,且可降低血清肿瘤标志物和E2水平,改善远期预后。     

McCune-Albright综合征患儿超说明书用药并文献复习

探讨甲羟孕酮、来曲唑和唑来膦酸超说明书用药的合理性。方法：1例6岁8个月男性患儿，出生时发现左臀部咖啡样色斑，4岁颅面部畸形，5岁时出现第二性征发育，同时出现骨龄超前，诊断为"McCune-Albright综合征"。入院后，相继给予甲羟孕酮片（4 mg bid po）+来曲唑片（1.25 mg qd po）+唑来膦酸注射液（3 mg once iv gtt）+碳酸钙片（250 mg qd po）和维生素AD滴剂（胶囊型）（1粒qdpo）治疗。结果：经过23 d的对症治疗后，患者一般情况及症状稳定，要求出院。结论：临床药师参与患者的药物治疗过程，对唑来膦酸和甲羟孕酮、来曲唑的超说明书用药有了进一步的认识，提高了药物的治疗水平。临床药师通过参与临床实践，协助医师参与患者的用药监护，提高药物治疗的安全性。     

Lapatinib nano-delivery systems: a promising future for breast cancer treatment

Introduction: Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation.

Areas covered: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose.

Expert opinion: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment.     

某院来曲唑超适应证用药循证医学评价分析

目的:基于循证医学方法对阜阳市人民医院(下称“我院”)来曲唑超适应证用药情况进行评价,并提出分级管理建议,为临床合理用药提供参考。方法:收集我院2021年6月至2022年5月使用来曲唑的门诊处方,初筛出超适应证用药处方。引用Micromedex数据库的Thomson分级系统对超说明书用药的收录结果,未收录的则检索相关指南和文献数据库。通过AGREEⅡ对检索的临床指南进行质量评价,AMSTAR 2量表和GRADE分级系统分别对纳入的系统评价/Meta分析的方法学质量和证据质量等级进行评价。判定超适应证有无循证医学证据并提出分级管理建议。结果:来曲唑超适应证涉及女性不孕症、体质性生长和青春发育延迟、多囊卵巢综合征、中枢性性早熟、生长激素缺乏症、月经不规则、男性不育症、男性乳房发育、子宫内膜癌、卵巢癌和卵巢过度刺激综合征11个诊断。根据Thomson分级系统,判定多囊卵巢综合征、体质性生长和青春发育延迟有循证医学证据,建议B级管理,限制使用;根据指南,判定女性不孕症、子宫内膜癌和卵巢癌有循证医学证据,建议B级管理,限制使用;其余均无循证医学证据,建议D级管理,禁止使用。结论:通过循证医学证据...     

The effects of letrozole and clomiphene citrate on ligands expression of Wnt3, Wnt7a,and Wnt8b in proliferative endometrium of women with Polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is a common endocrinologic disorder in women of reproductive age characterized by polycystic ovaries, oligo/anovulation, and hyperandrogenism. Not only anovulation but also endometrial dysfunction can reduce fertility in PCOS patients. Wnt pathway is responsible for endometrial proliferation which be strongly regulated by estradiol. To determine the effects of clomiphene citrate (CC) and letrozole, we measured the expression of some main ligands of Wnt/β-catenin signaling including Wnt7a, Wnt3, and Wnt8b in the endometrial samples taken from PCOS women on day 12 of the menses who received 100?mg CC or 5?mg letrozole as well as from women without treatment. Significantly, the mean estrogen and progesterone concentration were lower and higher, respectively, in letrozole than CC. The mean endometrial thickness (ET) was significantly greater in letrozole compared to CC. Assessment of the mRNA and protein expression of Wnt7a, Wnt3, and Wnt8b showed significantly lower expression in CC than the letrozole and control groups. Collectively, letrozole provided a better molecular response in the endometrium of PCOS patients during the proliferative phase, similar to natural cycles, compared to CC. CC decreased the ligands expression of Wnt3, Wnt7a, and Wnt8b, resulting in endometrial dysfunction.     

不同促排卵方案在多囊卵巢行体外受精-胚胎移植患者中的效果及对相关指标的影响

目的比较不同促排卵方案在多囊卵巢体外受精-胚胎移植(IVF-ET)患者中的效果及对相关指标表达的影响。方法选取56例多囊卵巢IVF-ET患者,随机分为A组(传统长效促性腺激素释放激素激动剂组)28例和B组(来曲唑组)28例。比较2组的促性腺激素(Gn)量、Gn时间、窦卵泡数、受精率、妊娠率、OHSS发生率及不同时间的抗苗勒氏管激素(AMH)水平、性激素水平。结果 B组的Gn量小于A组,Gn时间短于A组,窦卵泡数、受精率及妊娠率均高于A组,OHSS发生率低于A组,不同时间的AMH水平均高于A组,HCG日B组血清LH高于A组,血清E_2低于A组,移植日B组血清P低于A组,差异均有统计学意义(P0.05)。结论来曲唑在多囊卵巢IVF-ET患者中的效果较好,患者相关指标的表达状态也更好。     

Cost effectiveness of letrozole and purified urinary FSH in treating women with clomiphene citrate-resistant polycystic ovarian syndrome: a randomized controlled trial

We aimed to compare the cost effectiveness of letrozole versus purified urinary follicle stimulating hormone (FSH) in treating patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). This was a randomized trial conducted in Cairo University and Beni-Suef University Hospitals, Egypt. A cohort of 140 eligible women was randomized to receive either letrozole 2.5?mg twice daily for five days, or FSH using a graduated regimen starting with a dose of 75?IU. Treatment was repeated for three months if pregnancy did not occur. There were no significant differences between the two treatments in the cumulative clinical pregnancy rate (30% vs. 34%; p?=?0.578), cumulative ovulation rate (47% vs. 57%; p?=?0.236), miscarriage rate (9% vs. 4%, p?>?0.999) or multiple pregnancy rate (0% and 8%, p?=?0.491) but the FSH cycles were 4.8 times more expensive. Letrozole and FSH were both effective in treating women with CC-resistant PCOS but letrozole was more cost effective.Study registration number: NCT02304107.     

Preparation and characterization of letrozole-loaded poly(d,l-lactide) nanoparticles for drug delivery in breast cancer therapy

Letrozole (LTZ), an aromatase inhibitor used for the treatment of hormonally-positive breast cancer in postmenopausal women, has poor water solubility, rapid metabolism, and a range of side effects. In this study, polymer-based nanoparticles (NPs) incorporating the drug have been designed and characterized, aimed to control the release, potentially maximize the therapeutic efficiency, and minimize the side effects of the drug. LTZ was incorporated into poly(d,l-lactide) (PDLLA) NPs by employing the emulsion-solvent evaporation technique using a range of drug concentrations. Loaded drug and drug-polymer interactions were studied using X-ray diffraction and NPs morphology was evaluated using scanning electron microscopy (SEM). Particle size distribution (PSD) and zeta potential of the NPs were analyzed using dynamic light scattering (DLS) and laser Doppler velocimetry (LDV), respectively. Drug content and release profile studies were carried out and determined using ultra performance liquid chromatography (UPLC). The yield of LTZ-PDLLA NPs reached as high as 85%. The NPs were spherical and smooth, regardless of LTZ concentration in the formulation. However, particle size increased from 241.6?±?1.2 to 348.7?±?6.1?nm upon increasing LTZ concentration from 0 to 30% w/w, with entrapment efficiencies reaching up to 96.8%. Drug release from the polymeric matrix was best described by Higuchi model with a predominant diffusion-based mechanism. More than 15, 46, and 86% of LTZ was released in a controlled fashion over 30?d from the 10, 20, and 30% LTZ-PDLLA NPs, respectively. Overall, LTZ-PDLLA NPs were designed with appropriate size and surface charge, high drug loading, superior entrapment efficiency, and prolonged release profile.