In the Journals

Estrogen therapy timing influences age at menarche in Turner syndrome

In girls with Turner syndrome, a younger age at estrogen therapy initiation is associated with a longer time to menarche, whereas presence of a mosaic karyotype is associated with a shorter time to menarche, according to published findings.

Lisal J. Folsom, MD, a fellow in the section of pediatric endocrinology, Riley Hospital for Children, and the division of endocrinology and metabolism at Indiana University in Indianapolis, and colleagues evaluated medical records from 2007 to 2015 of 53 girls with Turner syndrome who had completed puberty (mean age at diagnosis, 6.4 years) to determine whether patient characteristics are associated with the timing of menarche.

“Primary ovarian failure occurs in greater than 80% of girls with [Turner syndrome], and [ET] is required for pubertal development with the subsequent addition of progesterone to induce menses. While standardized algorithms for hormone replacement therapy in girls with [Turner syndrome] are currently lacking, the goal is to simulate the timing and tempo of normal puberty as much as possible in order to achieve optimal psychosexual outcomes,” the researchers wrote. “It is currently unknown whether individual patient or treatment characteristics influence the time from the initiation of estrogen to menarche in these patients.”

Among the study cohort, 10 participants had reached menarche spontaneously, and the remaining participants received HT. A mosaic karyotype was found in 62.3% of participants, and 32.1% had a 45,X karyotype.

Mean age at estrogen initiation for the girls with primary ovarian failure was 13.9 years with a mean age at menarche of 15.7 years. A longer time to menarche was associated with a younger age at estrogen initiation (P = .02); a shorter time to menarche was associated with a mosaic karyotype (P = .02). No relationships were found between time to menarche and BMI z score, estrogen route or dose, maternal age at menarche or prenatal vs. postnatal diagnosis.

Among participants who started HT, 55.8% were treated with progesterone before experiencing menarche, and 44.2% experienced menarche on estrogen alone. More participants who reached menarche on estrogen alone were treated with transdermal estrogen compared with those who received additional treatment (P = .01).

Participants who required pubertal induction were older than those who experienced menarche spontaneously (P < .01).

“Our findings emphasize the broad spectrum of pubertal development in girls with [Turner syndrome] ranging from complete ovarian failure to spontaneous puberty and menarche,” the researchers wrote. “They also confirm that girls with mosaic [Turner syndrome] are significantly more likely to undergo spontaneous menarche than those with 45,X karyotypes. Furthermore, the wide range of estrogen doses being prescribed at the time of menarche in girls with induced puberty emphasizes the extreme variability in estrogen sensitivity in these patients. This suggests that estrogen titration should be guided in part by individual responses and evaluated on an ongoing basis in conjunction with patients and families over time. Our results should help to inform decisions regarding timing of estrogen initiation and provide important prognostic information for families and providers who care for girls with [Turner syndrome].” – by Amber Cox

Disclosure: The researchers report no relevant financial disclosures.

In girls with Turner syndrome, a younger age at estrogen therapy initiation is associated with a longer time to menarche, whereas presence of a mosaic karyotype is associated with a shorter time to menarche, according to published findings.

Lisal J. Folsom, MD, a fellow in the section of pediatric endocrinology, Riley Hospital for Children, and the division of endocrinology and metabolism at Indiana University in Indianapolis, and colleagues evaluated medical records from 2007 to 2015 of 53 girls with Turner syndrome who had completed puberty (mean age at diagnosis, 6.4 years) to determine whether patient characteristics are associated with the timing of menarche.

“Primary ovarian failure occurs in greater than 80% of girls with [Turner syndrome], and [ET] is required for pubertal development with the subsequent addition of progesterone to induce menses. While standardized algorithms for hormone replacement therapy in girls with [Turner syndrome] are currently lacking, the goal is to simulate the timing and tempo of normal puberty as much as possible in order to achieve optimal psychosexual outcomes,” the researchers wrote. “It is currently unknown whether individual patient or treatment characteristics influence the time from the initiation of estrogen to menarche in these patients.”

Among the study cohort, 10 participants had reached menarche spontaneously, and the remaining participants received HT. A mosaic karyotype was found in 62.3% of participants, and 32.1% had a 45,X karyotype.

Mean age at estrogen initiation for the girls with primary ovarian failure was 13.9 years with a mean age at menarche of 15.7 years. A longer time to menarche was associated with a younger age at estrogen initiation (P = .02); a shorter time to menarche was associated with a mosaic karyotype (P = .02). No relationships were found between time to menarche and BMI z score, estrogen route or dose, maternal age at menarche or prenatal vs. postnatal diagnosis.

Among participants who started HT, 55.8% were treated with progesterone before experiencing menarche, and 44.2% experienced menarche on estrogen alone. More participants who reached menarche on estrogen alone were treated with transdermal estrogen compared with those who received additional treatment (P = .01).

Participants who required pubertal induction were older than those who experienced menarche spontaneously (P < .01).

“Our findings emphasize the broad spectrum of pubertal development in girls with [Turner syndrome] ranging from complete ovarian failure to spontaneous puberty and menarche,” the researchers wrote. “They also confirm that girls with mosaic [Turner syndrome] are significantly more likely to undergo spontaneous menarche than those with 45,X karyotypes. Furthermore, the wide range of estrogen doses being prescribed at the time of menarche in girls with induced puberty emphasizes the extreme variability in estrogen sensitivity in these patients. This suggests that estrogen titration should be guided in part by individual responses and evaluated on an ongoing basis in conjunction with patients and families over time. Our results should help to inform decisions regarding timing of estrogen initiation and provide important prognostic information for families and providers who care for girls with [Turner syndrome].” – by Amber Cox

Disclosure: The researchers report no relevant financial disclosures.