Vegetti W, Marozzi A, Manfredini E, Testa G, Alagna F, Nicolosi A, Caliari I, Taborelli M, Tibiletti M G, Dalprà L, Crosignani P G
First Department of Obstetrics and Gynaecology, University of Milan, Via della Commenda 12, 20122, Milan, Italy.
Mol Cell Endocrinol. 2000 Mar 30;161(1-2):53-7. doi: 10.1016/s0303-7207(99)00224-5.
Secondary amenorrhoea with elevated gonadotrophins occurring under the age of 40 (premature ovarian failure (POF)), and at the age between 41 and 44 years (early menopause (EM)), respectively, affects 1-2% and 5% of women in the general population. Objective of this study was to evaluate the prevalence of familial cases of POF and EM and to assess the clinical and genetic characteristics of these patients. One hundred and sixty women with idiopathic secondary amenorrhoea before the age of 45 and serum follicle-stimulating hormone (FSH) levels greater than or equal to 40 IU/l were included in the study. Tests performed on patients included complete medical history, pedigree's analysis, clinical pelvic examination, gonadotrophins and thyroid assessment, chromosomal analysis. The 160 patients included in the study showed idiopathic POF (n=130) or EM (n=30). Following pedigree assessment, we were able to identify an incidence of familial cases of 28.5% in the POF group (n=37) and of 50% in the EM group (n=15). POF and EM condition were often present in the same family. There were no differences between POF and EM patients and between familial and sporadic cases regarding age at menarche, personal history, gynaecological history, weight, height and diet habits. There was a statistically significant difference between sporadic and familial cases in age at POF onset: 32.0+/-7.3 years (12-40) compared to 35. 0+/-5.8 (18-40), respectively (P<0.05). The POF and EM families identified showed two or more affected females and transmission through either maternal or paternal relatives; in four families both maternal and paternal transmission was observed. This study suggests that idiopathic POF and EM conditions, differing only in age of menopause onset, may represent a variable expression of the same genetic disease. The different age of menopause onset in these patients may be explained by genetic heterogeneity and/or by different environmental factors. Our results indicate a high rate of familial transmission of the condition. Pedigree's analysis suggests an autosomal or an X-linked dominant sex-limited pattern of inheritance for POF and EM.
40岁以下出现继发性闭经且促性腺激素升高（卵巢早衰（POF））以及41至44岁之间出现这种情况（早期绝经（EM）），分别影响普通人群中1%-2%和5%的女性。本研究的目的是评估POF和EM家族性病例的患病率，并评估这些患者的临床和遗传特征。本研究纳入了160名45岁之前患有特发性继发性闭经且血清促卵泡生成素（FSH）水平大于或等于40 IU/L的女性。对患者进行的检查包括完整的病史、家系分析、临床盆腔检查、促性腺激素和甲状腺评估、染色体分析。纳入研究的160名患者表现为特发性POF（n=130）或EM（n=30）。经过家系评估，我们发现在POF组中家族性病例的发生率为28.5%（n=37），在EM组中为50%（n=15）。POF和EM情况经常出现在同一个家族中。在初潮年龄、个人史、妇科病史、体重身高和饮食习惯方面，POF和EM患者之间以及家族性和散发性病例之间没有差异。POF发病年龄的散发性和家族性病例之间存在统计学显著差异：分别为32.0±7.3岁（12-40岁）和35.0±5.8岁（18-40岁）（P<0.05）。所识别的POF和EM家族中有两名或更多受影响的女性，且通过母系或父系亲属遗传；在四个家族中观察到了母系和父系遗传。本研究表明特发性POF和EM情况，仅在绝经起始年龄上有所不同，可能代表同一种遗传疾病的不同表现形式。这些患者绝经起始年龄的差异可能由遗传异质性和/或不同的环境因素来解释。我们的结果表明该疾病的家族遗传率很高。家系分析表明POF和EM的遗传模式为常染色体或X连锁显性性别限制遗传。
