Sunday, June 04, 2006

Lourdes Ibañez, Menarche and Low Birth Weight

I am currently looking at lower age at menarche, speed of transition to the lower ages, and fertility impacts. The big conjecture would be that there should be a negative impact of this process on final achieved TFRs in the context of a systematic and continuing birth postponment process. To date I have nothing conclusive on this one way or the other.

However I have identified two secondary feedback mechanisms which do seem to influence long term fertility:

a) A correlation between obesity and lowest low menarche. Now obestity is also a fertility inhibiting correlate.

b) A relationship between reduced birth weight, lower age at menarche (due to subsequent cath-up growth) and reduced lifelong fertility.

Here the work of Lourdes Ibañez seem to be very important:

Early Puberty-Menarche After Precocious Pubarche: Relation to Prenatal Growth
Lourdes Ibáñez, MD, PhDa, Rafael Jiménez, MD, PhDa and Francis de Zegher, MD, PhDb

RESULTS. At the time of PP diagnosis, age, bone age, and BMI were similar across birth weight subgroups; circulating sex hormone–binding globulin and body height were reduced in PP girls with lower birth weight, and these remained so throughout pubertal development. Onset of puberty occurred earlier in PP girls with lower birth weight; so did menarche. Adult height differed by an average of 6.5 cm (~1 SD) between the upper and lower birth weight subgroups; this difference was essentially achieved before puberty and even before PP. Menarche before age 12.0 years was twofold more prevalent in PP girls than in control subjects. Among PP girls, age at menarche was advanced by 8 to 10 months in lower versus higher birth weight girls. Menarche before age 12.0 years was threefold more prevalent among LBW-PP girls than in control subjects (~75% vs ~25%).

CONCLUSIONS. The link between prenatal growth restraint and early menarche is herewith extended to PP girls. In particular LBW-PP girls may become a target group for interventions directed toward normalization of pubertal onset and progression.

Reduced Ovulation Rate in Adolescent Girls Born Small for Gestational Age

Lourdes Ibáñez, Neus Potau, Angela Ferrer, Francisco Rodriguez-Hierro, Maria Victoria Marcos and Francis de Zegher

Interestingly for the bigger issue Lourdes here finds a more rapid ovulation rate in post menarche children than previously reported:

"This is a first study assessing adolescent ovulation rate over 3 months, on an ambulatory basis, through weekly measurements of progesterone concentrations in capillary blood dried on filter paper. With this novel method, 23 of 24 participating AGA (appropriate for gestational age) girls were found to have at least one ovulatory cycle within 3 months. This ovulation rate (96%) is, so far, the highest reported in adolescents (16, 17), suggesting that this technique has a sensitivity superior to previous methods (17). Moreover, it is unlikely that this simple method overestimates ovulation rate because the time lag between the proposed ovulation date and the onset of the following menses was uniformly consistent with the time course of a normal ovulatory cycle."


"The ovulation rate in SGA (small for gestational age) girls was found to be strikingly low; the anovulatory fraction was much larger than in the AGA girls. Moreover, in ovulatory SGA girls, the individual number of ovulations over 3 months was also reduced. Interestingly, the reduction in ovulation rate was comparable in SGA adolescents who had reached a stature within target range and in SGA girls with a postmenarcheal stature that was below target level. This observation suggests that anovulation secondary to prenatal growth restraint is a phenomenon that is essentially unrelated to completeness of spontaneous catch-up growth. Thus, in SGA girls, spontaneous recovery of linear growth during childhood does not warrant normal ovulatory function in adolescence; conversely, persistent growth failure in SGA girls will not necessarily be followed by anovulation."

"That the link between reduced prenatal growth and anovulation has apparently escaped attention for so long may in part be attributable to the fact that the majority of SGA girls normalize their stature, and hereby no longer present an obvious reminder of their early growth restraint. The copresence of obesity may have been another notoriously confounding factor in ovulation research; the absence of obesity in the described study population has presumably facilitated the disclosure of the link between prenatal growth and postmenarcheal ovulation rate."

"Prenatal growth restraint has previously been documented to be associated with relative hyperinsulinism, hyperandrogenism, and FSH hypersecretion in adolescent girls from Catalunya (5, 18, 19). These associations were confirmed in the present cohort and may each contribute to the reduced ovulation rate in SGA adolescents."

Ibáñez L, Potau N, de Zegher F 2000 Ovarian hyporesponsiveness to follicle stimulating hormone in adolescent girls born small for gestational age. J Clin Endocrinol Metab 85:2624–2626

Ibáñez L, Potau N, Marcos MV, de Zegher F 1999 Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age. J Clin Endocrinol Metab 84:4739–4741

Ibáñez L, Valls C, Miró E, Marcos MV, de Zegher F Early menarche and subclinical ovarian hyperandrogenism in girls with reduced adult height after low birthweight. J Pediatr Endocrinol Metab 15:431–433

Ibáñez L, Valls C, Ferrer A, Ong K, Dunger D, de Zegher F 2002 Additive effects of insulin-sensitizing and anti-androgen treatment in young, non-obese women with hyperinsulinism, hyperandrogenism, dyslipidemia and anovulation. J Clin Endocrinol Metab 87:2870–2874

"In conclusion, the endocrine correlates of prenatal growth restraint are herewith extended to include oligo-ovulation and anovulation in adolescence. It remains to be verified whether this SGA-related phenomenon persists into the reproductive age range. If it does, then fetal growth restraint may prove to be one of the enigmatic components underpinning hitherto unexplained female subfertility."

Here's a page summarising Lourdes's work (in Catalan).

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