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青少年多囊卵巢综合征的月经周期模式、体重指数、内分泌及卵巢超声特征与未来生育能力、心血管和代谢健康:一项25年的纵向随访研究

Adolescent menstrual cycle pattern, body mass index, endocrine and ovarian ultrasound characteristics of PCOS and future fertility, cardiovascular-, and metabolic health: a 25-year longitudinal follow-up study.

作者信息

van Hooff Machiel H A, Caanen Mirte R, Peters Henrike E, Laven Joop S E, Lambalk Cornelis B

机构信息

Department of Obstetrics and Gynaecology, Franciscus Gasthuis en Vlietland, Rotterdam, The Netherlands.

Department of Reproductive Medicine, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands.

出版信息

Hum Reprod. 2025 Jan 1;40(1):138-147. doi: 10.1093/humrep/deae262.

Abstract

STUDY QUESTION

What is the predictive value of oligomenorrhea and other PCOS diagnostic characteristics in adolescence (age 15-18 years) for future fertility and cardiovascular and metabolic health at adult age?

SUMMARY ANSWER

Adolescents with oligomenorrhea are more often treated to conceive but are as likely to have as much children as those with regular periods, while persisting oligomenorrhea may associate more often with cardiovascular or metabolic problems.

WHAT IS KNOWN ALREADY

Adolescents with oligomenorrhea have a high risk for adult PCOS associated with subfertility due to ovulatory disorders and long-term health risks. Longitudinal studies to estimate the extent of these risks with input starting at adolescence and covering the complete reproductive lifespan are lacking.

STUDY DESIGN, SIZE, DURATION: A 25-year prospective follow-up study based on a unique population-based adolescent study on menstrual irregularities performed between 1990 and 1997, the Pubertal Onset of Menstrual Cycle abnormalities, a Prospective study (POMP study). Of the 271 invited adults, 160 (59%) participated.

PARTICIPANTS/MATERIALS, SETTING, METHODS: We contacted stratified samples of the POMP study cohort two decades after the initial study for a questionnaire assessing PCOS features, fertility history, pregnancy outcome, metabolic, and cardiovascular health. One hundred and sixty subjects completed the questionnaire. The mean adolescent age was 15.3 years, and the women were 39.6 years at the time of follow-up. One hundred and eight subjects had a regular menstrual cycle as adolescents and 52 were oligomenorrheic.

MAIN RESULTS AND THE ROLE OF CHANCE

Of those with adolescent regular menstrual cycles 12 never tried to conceive, 4 tried but never conceived and 92 of 96 (96%) conceived, 89 of 96 (93%) delivering at least one living child. The median number of children was two. The mean time to pregnancy (TTP) was 8.4 months in the women with regular periods as adolescents and 13.2 months in case of oligomenorrhea (P = 0.08) and subfertility was present in respectively 18% and 26%. 47 of 52 adolescents with oligomenorrhea tried to conceive and 45 succeeded to have at least one live birth. Twenty-eight per cent of the subjects reported a change over time of their menstruation pattern. Fifty per cent of the girls with adolescent oligomenorrhea developed a regular cycle and 16% of those with regular periods changed to oligomenorrhea with significantly more reported subfertility (40%, P = 0.04). In case of persistent oligomenorrhea, a significant proportion (40%) underwent fertility treatment (P = 0.04). Adult BMI did not differ between groups. The risk for pregnancy-induced hypertension or pre-eclampsia was comparable between the groups. Gestational diabetes developed in three subjects each with persistent oligo amenorrhea. Adult diabetes, hypertension, and hypercholesterolemia were also mostly reported in case of persistent oligomenorrhea. In this group, the prevalence of combined cardiovascular and metabolic problems was 14% compared to 7% in the case of regular menstrual cycles as adolescent.

LIMITATIONS, REASONS FOR CAUTION: The numbers in the study are small. However, the small difference between the percentage with a least one living child of those with adolescent oligomenorrhea versus those with adolescent regular menstrual cycles is reassuring. Time to pregnancy data may have been biased by early treatment of oligomenorrheic adults.

WIDER IMPLICATIONS OF THE FINDINGS

Oligomenorrheic adolescents may be reassured that their chance to have a live birth is comparable with those with a regular menstrual cycle.

STUDY FUNDING/COMPETING INTEREST(S): This research received no external funding, J.S.E.L. received unrestricted research grants from the following companies (in alphabetical order): Ansh Labs, Ferring, Merck, and Roche Diagnostics. He received consultancy fees or royalties from Ansh Labs, Art pred, Ferring, Gedeon Richter, and Roche Diagnostics. He received presentation fees from Ferring and Roche Diagnostics as well as support for attending meetings and/or travel from Ferring and Roche Diagnostics and he participated in the advisory board of the LOCI Trial UK.

TRIAL REGISTRATION NUMBER

Dutch Trial Registry, NTR5871.

摘要

研究问题

青春期(15 - 18岁)的月经过少及其他多囊卵巢综合征(PCOS)诊断特征对成年后的生育能力、心血管和代谢健康有何预测价值?

总结答案

月经过少的青少年更常接受治疗以受孕,但生育子女数量与月经规律者相当,而持续性月经过少可能更常与心血管或代谢问题相关。

已知信息

月经过少的青少年因排卵障碍和长期健康风险,患成人PCOS及生育力低下的风险较高。缺乏从青春期开始并涵盖整个生殖寿命期来评估这些风险程度的纵向研究。

研究设计、规模、持续时间:一项基于1990年至1997年进行的一项独特的基于人群的青少年月经不规律研究——青春期月经周期异常的前瞻性研究(POMP研究)的25年前瞻性随访研究。在271名受邀成年人中,160名(59%)参与了研究。

参与者/材料、设置、方法:在初始研究二十年后,我们联系了POMP研究队列的分层样本,通过问卷调查评估PCOS特征、生育史、妊娠结局、代谢和心血管健康。160名受试者完成了问卷。青少年的平均年龄为15.3岁,随访时女性年龄为39.6岁。108名受试者在青少年时期月经周期规律,52名月经过少。

主要结果及机遇的作用

青少年月经周期规律者中,12人从未尝试受孕,4人尝试但未受孕,96人中92人(96%)受孕,96人中89人(93%)产下至少一个存活婴儿。子女数量中位数为2个。青少年时期月经规律的女性平均受孕时间(TTP)为8.4个月,月经过少者为13.2个月(P = 0.08),生育力低下发生率分别为18%和26%。52名月经过少的青少年中有47人尝试受孕,45人成功产下至少一个存活婴儿。28%的受试者报告其月经模式随时间发生了变化。青少年月经过少的女孩中有50%月经周期变得规律,月经规律者中有16%变为月经过少,且报告的生育力低下情况明显更多(40%,P = 0.04)。对于持续性月经过少,相当比例(40%)接受了生育治疗(P = 0.04)。各组成人BMI无差异。各组妊娠高血压或先兆子痫风险相当。持续性月经过少的受试者中各有3人发生妊娠期糖尿病。成人糖尿病、高血压和高胆固醇血症也大多在持续性月经过少的情况下报告。在这一组中,心血管和代谢问题合并发生率为14%,而青少年时期月经周期规律者为7%。

局限性、谨慎理由:研究样本量较小。然而,青少年月经过少者与青少年月经周期规律者中至少有一个存活婴儿的比例差异较小,令人安心。受孕时间数据可能因月经过少的成年人早期治疗而存在偏差。

研究结果的更广泛影响

月经过少的青少年可放心,其产下存活婴儿的机会与月经周期规律者相当。

研究资金/利益冲突:本研究未接受外部资金,J.S.E.L. 从以下公司(按字母顺序排列)获得无限制研究资助:安时实验室、辉凌、默克和罗氏诊断。他从安时实验室、Art pred、辉凌、吉德昂·里奇特和罗氏诊断获得咨询费或版税。他从辉凌和罗氏诊断获得演讲费,以及辉凌和罗氏诊断提供的参加会议和/或旅行支持,他还参与了英国LOCI试验的顾问委员会。

试验注册号

荷兰试验注册中心,NTR5871。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ede1/11700892/291b5af2f40f/deae262f1.jpg

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