Anti-goat antibodies as a rare cause of high gonadotropin levels during menopausal transition

Abstract

Objective: To understand the origin of extremely high gonadotropin levels in a perimenopausal woman.

Methods: A 52-year-old woman with a 2?months of amenorrhea followed spontaneous menstrual cycles recovery was referred to our outpatient clinic with elevated follicle-stimulating hormone (FSH, 483 mUI/ml), luteinizing hormone (LH, 475 mUI/ml) and prolactin (PRL, 173?ng/ml). She was known to take levosulpiride. The gonadotropin levels did not fit with the clinical features.

Results: A gonadotroph tumor was ruled out. Further analysis confirmed constantly high FSH, LH and PRL levels. The measurements were repeated using different analytical platforms with different results. After serial dilutions, nonlinearity was present suggesting an immunoassay interference. After post-polyethylene glycol recovery, hormone levels appeared in the normal range. Anti-goat antibodies were recognized in the serum of the patient.

Conclusions: This case report shows a case of falsely abnormal high gonadotropin and PRL levels in a woman during menopause transition. In the clinical practice the evaluation of gonadotropin profile is not recommended at this age, but the abnormal levels stimulated further evaluation. An interference in the assay due to anti-goat antibodies resulted in abnormally high level of FSH and LH. A strict collaboration between clinicians and the laboratory is needed, when laboratory findings do not correspond to clinical findings.     

探讨绝经过渡期、育龄子宫肌瘤患者异常阴道出血相关因素分析

目的: 探讨育龄、绝经过渡期子宫肌瘤患者异常阴道出血危险因素，为异常阴道出血临床精准诊断、治疗提供理论依据。方法： 选取2017年06月—2020年06月于内蒙古医科大学附属医院住院行手术治疗的子宫肌瘤患者。实验组设为非月经期异常阴道出血的子宫肌瘤患者，对照组为无异常阴道流血子宫肌瘤患者。根据第9版教科书年龄18-43岁定为育龄组；44-54岁定为绝经过渡期组（我国妇女平均绝经年龄为49.5岁，80%在44-54岁之间〔1〕）。 应用Excel双录入，核对无误后进行统计分析。计数资料的比较用R×C列联表卡方检验、四格表卡方检验及两独立样本秩和检验。非条件Logistic回归模型用于子宫肌瘤阴道异常出血危险因素的分析，并分别得到OR值与相应95%的可信区间。在此模型中，OR值＞1认为是危险因素，OR值＜1认为是保护因素。统计学显著性水平设定为双侧p≤0.05，即认为差异有统计学意义。全部统计分析选用SPSS19.0软件进行统计学分析。结果：1.将与子宫肌瘤阴道异常出血相关的33项临床指标纳入单因素分析得出，月经周期异常、肌瘤位置（子宫颈肌瘤）、肌瘤直径≥9cm、血红蛋白异常、子宫内膜癌、核分裂像＞5个差异有统计学意义（P≤0.05），均是子宫肌瘤阴道异常出血的危险因素；2.子宫肌瘤异常阴道出血核分裂像＞5个与子宫内膜病理性改变和异常阴道出血差异有统计学意义（P=0.019）。结论：1. 子宫内膜发生病理改变是子宫肌瘤患者引起异常阴道出血的原因之一。2.月经周期异常、子宫颈肌瘤、肌瘤直径≥9cm、血红蛋白异常、子宫内膜病理改变均是子宫肌瘤阴道异常出血的危险因素；子宫肌瘤核分裂像＞5个是子宫平滑肌瘤出现异常阴道出血的独立高危因素；3.子宫肌瘤核分裂像＞5与阴道出血、子宫内膜病理改变有统计学意义。进行单因素分析后得知，月经周期、肌瘤位置、肌瘤大小、血红蛋白、子宫内膜病理变化均子宫肌瘤阴道异常出血的发生有关。 关键词育龄；绝经过渡期；子宫平滑肌瘤；异常阴道出血；危险因素     

Prevention of early postmenopausal bone loss using low doses of conjugated estrogens and the non-hormonal,bone-active drug ipriflavone

Hormone replacement therapy is the optimal therapeutic choice for postmenopausal syndrome. While low doses of estrogens (0.3 mg/day of conjugated estrogens) can counteract neurovegetative menopausal symptoms, higher doses (0.625 mg/day of conjugated estrogens) are required to prevent bone loss in postmenopausal women. Experimental and clinical studies have shown that ipriflavone, a non-hormonal isoflavone derivative, is effective in the prevention and treatment of postmenopausal osteoporosis. The aim of the present investigation was to evaluate the efficacy and toler-ability of ipriflavone and very low doses of equine conjugated estrogens on bone loss in early postmenopausal women. Eighty-three healthy postmenopausal women (50.3±0.7 years) were enrolled for this 1-year multicenter study. All subjects were randomly allocated to receive: double placebo (n=24; group A), placebo plus conjugated equine estrogens 0.30 mg/day (n=31; group B) or conjugated equine estrogens 0.30 mg/day plus oral ipriflavone 200 mg tris in die at meals (n=28; group C), according to a double-masked design. Among women who completed the treatment period (valid completers), those of group A showed a progressive decrease in forearm bone density (FBD; measured by dual photon absorptiometry) that reached 1.7% after 12 months. The women in group B maintained their FBD in the first 6 months of treatment but, at the end of the study, showed a bone loss of 1.4% compared with basal values. By contrast, women in group C showed a significant increase in FBD after 1 year of treatment (+5.6%;p<0.01). Bothvalid completers andintention to treat analyses revealed a significant difference (p<0.05) between group A and group C over the study period. None of the treatments produced significant changes of biochemical markers of bone turnover, while hot flushes and other climacteric symptoms were significantly reduced after the sixth month of treatment in women receiving estrogens. Adverse events were generally mild, and did not differ among the groups. The results of this study suggest that low doses of estrogens combined with ipriflavone could represent a new therapeutic approach to the treatment of the postmenopausal syndrome.     

Efficacy and tolerability of estraderm MX, a new estradiol matrix patch

Objectives: To assess the efficacy and tolerability of a new matrix patch delivering 0.05 mg estradiol per day (Estraderm MX 50) in postmenopausal women with moderate to severe postmenopausal symptoms. Methods: A multicenter, double-blin, randomized, between-patient, placebo controlled trial in 109 postmenopausal women was carried out. Patches were applied twice weekly for 12 weeks. Patients were assessed at 4, 8 and 12 weeks of treatment. The primary efficacy variable was change from baseline in mean number of moderate to severe hot flushes (including night sweats) per 24 h during the last 2 weeks of treatment. Other variables included Kupperman Index, local and systemic tolerability. Plasma concentrations of estradiol (E2), estrone (E1) and estrone sulfate (E1S) were determined before and after treatment. Results: Estraderm MX was significantly superior to placebo (P < 0.001) in reducing mean number of moderate to severe hot flushes (including night sweats) per 24 h after 4, 8 and 12 weeks of treatment. The estimate of treatment group differences after 12 weeks was 4.2 hot flushes (95% confidence interval: 2.6–5.5). Estraderm MX also significantly reduced Kupperman Index at all time points compared to placebo (P < 0.001). Estraderm MX induced increases in mean E2, E1 and E1S plasma levels as expected (E2: baseline 2.7 pg/ml, 12 weeks 38.9 pg/ml; E1: baseline 18.8 pg/ml, 12 weeks 41.6 pg/ml; E1S: baseline 235.6 pg/ml, 12 weeks 765.1 pg/ml). Overall rates of adverse experiences were similar for Estraderm MX and placebo. The number of patients reporting skin irritation was low and similar in both groups. Conclusions: Estraderm MX 50, a new matrix patch, offers an effective and well tolerated dosage form for transdermal delivery of 0.05 mg E2 per day.     

The effect of tibolone versus continuous combined norethisterone acetate and oestradiol on memory, libido and mood of postmenopausal women: a pilot study

Objective: Several studies have shown a positive effect of oestrogen on memory, mood and well-being but these data are controversial and focus particularly on the effect of oestrogen alone. In this pilot study we have investigated the effect of a continuous combination of norethisterone acetate 1 mg and oestradiol valerate 2 mg (Kliogest®) versus tibolone (Livial®) on memory, sexuality and mood. Methods: Twenty-two postmenopausal women, age range 51–57, were randomised to a 6 months single blind interventional study treatment with either continuous combined oestradiol plus norethisterone acetate, or tibolone. Computerised psychological test of memory, mood and libido were administered both before and at the end of the 6 months treatment. Results: Fourteen patients completed the study; eight on Livial® and six on Kliogest®. Recognition memory was improved by Kliogest but not by Livial (P<0.05) while either drug equally improved both the reaction time (P<0.01) and accuracy of performance (P<0.001) of categorical semantic memory. Both the treatments improved libido significantly (P<0.05), while the mood did not change with either. Conclusion: The results suggest that both these forms of hormonal replacement therapy improve the efficiency of memory performance and libido. However, a combination of oestradiol and norethisterone acetate seems to be marginally more effective on improving cognitive processes.     

200例更年期综合征妇女精神心理及社会因素现况调查

目的：了解更年期综合征患者精神和心理障碍,探讨社会因素对其的影响,方法：通过问卷式表格填写的方法,对200例更年期综合征妇女进行进行躯体表现、精神和心理障碍,应激反应、性生活、应激事件等现况调查,结果：更年期货征妇女普遍存在精神心理障碍,65％应激反应下降,50％性功能下降,生活中应激事件与更年期的综合征互为影响,结论：提高这一人群的生命质量,激素替代治疗须配合心理支持治疗。     

药食两用中药复方对去卵巢大鼠内分泌激素的影响

目的：探讨药食两用中药复方治疗绝经期综合征的作用机理。方法：以去卵巢大鼠为动物模型，已烯雌酚片为阳性对照药物，采用放射免疫测定法观察该复方对血清E2，FSH，LH，T，P，T3，T4及TSH等激素水平的影响。结果：与去卵巢空白对照组比较，该中药复方能升高血清E2值，降低血清FSH，LH，T3，T4值，差异均有显著性（P〈0．05）。结论：该中药复方能多途径调节卵巢大鼠生殖内分泌功能，改善甲状腺功能。提示其能够稳定机体内环境，缓解绝经期综合征症状。     

绝经期抑郁症3种治疗方案的比较

目的:探讨氟西汀联合结合雌激素加甲羟孕酮(倍美盈),治疗绝经期抑郁症的疗效。方法:将106例绝经期抑郁症的妇女随机分3组。合用组39例:每日口服倍美盈和氟西汀各1粒:氟西汀组36例:每日口服氟西汀1粒;激素补充治疗(HRT)组31例:每日口服倍美盈1粒。疗程均8周。采用Ham ilton抑郁量表(HAMD)评价抑郁严重程度,采用Kupper-m an评分指数(KM l)评价绝经期症状。结果:治疗前后合用组、氟西汀组、HRT组HAMD总分分别为(23.01±3.54)、(4.98±4.48),(23.02±4.38)、(6.97±5.44),(23.04±4.56)、(10.01±5.75)。治疗后与治疗前比较3组总分均下降,差异有非常显著性(P<0.01)。治疗前后合用组、氟西汀组、HRT组KM I评分指数分别为(32.10±7.42)、(7.57±4.64),(31.83±7.65)、(16.09±6.06),(32.01±7.29)、(9.70±7.02),治疗后与治疗前比较3组总分均下降,差异有非常显著性(P<0.001)。但合用组和HRT组与氟西汀组比较减分率更高,差异有非常显著性(P<0.01)。结论:合用氟西汀和倍美盈治疗发生于绝经期的抑郁症,可以显著提高对抑郁症状的疗效。     

激素治疗对绝经妇女子宫肌瘤的影响

目的:观察个体化周期序贯激素治疗对绝经妇女子宫肌瘤发生及生长的影响。方法:选择因绝经相关症状且合并单发性子宫肌瘤(肌瘤最大径线<5 cm)的绝经妇女60例,给予雌孕激素周期序贯方案,起始剂量为口服戊酸雌二醇1.0 mg,每日1次,连用21~25天,后10~14天加用甲羟孕酮每日4 mg。随后,根据每人对药物的不同反应,调整口服戊酸雌二醇的每日用量为0.5~2.0 mg,甲羟孕酮的每日用量相应为4~6 mg。不能连续应用激素治疗或失访者被排除。分别于治疗前及治疗3、6、122、43、6个月时采用阴道超声测定肌瘤大小及子宫内膜厚度。结果:53例患者完成了3年的观察,平均年龄51.4(44~57)岁,绝经年限平均2.3(1~7)年。激素周期序贯治疗3、6、12、24、36个月,肌瘤大小均无明显改变(P>0.05),没发现新生肌瘤(P>0.05),子宫内膜厚度均无明显增厚(P>0.05)。结论:根据个体对药物反应不同制定不同剂量的激素周期序贯方案,不促进绝经妇女子宫肌瘤的发生和生长。     

Changes in cardiovascular risk profile in women after menopause (Prague Pre and Post Menopausal Female study)

IntroductionAtherosclerosis is the main cause of mortality in the Czech Republic. In our previous cross-sectional studies, we detected a high prevalence of metabolic cardiovascular risk factors in women before and after menopause and found menopausal transition to be critical period for atherosclerosis acceleration. In the present longitudinal study, we studied changes of main cardiovascular risk factors in women after transition to menopause.MethodsWe analyzed data of 195 women who became menopausal and 292 women who stayed in menopause during 6-year period. The cardiovascular risk factors under study were as follows: smoking, body mass index, waist circumference, blood pressure, plasma lipids including apolipoprotein B and A1 and fasting glycemia.ResultsThe most striking differences between newly and steadily menopausal women were found in changes of plasma lipids. With the exception of HDL cholesterol all changes were less favorable in newly menopausal women and were not associated with treatment with statins. No significant differences between both groups were found for changes in body mass index, waist circumference, blood pressure and fasting glycemia.ConclusionsIn longitudinal study we confirmed that time around menopausal transition is one of the most dynamic periods regarding changes of cardiovascular risk factors, mainly plasma lipids.