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

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.