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Women with a history of idiopathic precocious puberty had increased rates of clinical hyperandrogenism, but fertility was normal in adulthood among those who had been treated for the condition, a cross-sectional study found.
Those who had been treated with a gonadotropin-releasing hormone (GnRH) analog more often reported hyperandrogenism than matched controls (29.6% versus 17.4%, P=0.006), as did those who had received the older therapy cyproterone acetate (50% versus 20.4%, P=0.04), and those who were untreated (34.4% versus 17.2%, P=0.003), according to Liora Lazar, MD, and colleagues from the in Petah Tikva.
Action Points
- Women with a history of idiopathic precocious puberty had increased rates of clinical hyperandrogenism, but fertility was normal in adulthood among those who had been treated for the condition.
- In a logistic regression analysis, the treatment group was the only factor associated with hyperandrogenism with oligomenorrhea for women with untreated precocious puberty.
Yet rates of spontaneous pregnancy were equivalent for those who received GnRH analog treatment and controls (90.4% versus 93.4%) as well as for those treated with cyproterone acetate (CyA) and controls (86.7% versus 90.2%),
Premature sexual development originally was treated with oral progestational agents such as CyA, but this subsequently was replaced with injectable GnRH analogs in the 1980s, and many studies have demonstrated efficacy and safety of the treatment.
However, there are few long-term data on social adjustment and reproduction in adult life among women with central precocious puberty (CPP), and the studies that have been done were hampered by small numbers, lack of controls, and inadequate follow-up times.
To address this gap, Lazar's group reviewed the records and interviewed 214 women ages 25 to 56 who had been evaluated at their institution between 1975 and 2005.
Women who had received the GnRH analog were younger at the time of the interview, averaging 30 years of age, while those who had been given CyA were 42 and those who were untreated were 35, so the three groups each had separate age-matched control groups.
The GnRH analog group included 135 women, the CyA group consisted of 18, and the remaining 61 had not been treated. A total of 446 unaffected women served as controls.
Fewer of the GnRH analog group were married and had children, but this could be explained by the fact that they were younger, according to the researchers.
For instance, 68% of GNRH analog-treated women were married and 19% had three children, compared with 72% and 46% in the CyA-treated group.
No differences were seen among treated and untreated women or controls in educational attainment.
The age at onset of puberty was at about 7 years, and the age at menarche was 12 for treated girls and 11 for those not treated, which was a significant difference (P<0.001).
At the time they were interviewed, 30% of women with precocious puberty and controls were using oral contraceptives, with three-quarters of users being younger than 30.
The reason for oral contraceptive use was for birth control in 65% of affected women compared with 89% of controls, while irregular menstruation and/or hyperandrogenism was the reason in 35% of affected women and 11% of controls (P<0.001).
One-third of women with precocious puberty had hyperandrogenism, characterized by hirsutism and/or acne, and 22% also reported oligomenorrhea.
In a logistic regression analysis with variables including chronological age at the beginning of puberty, age at menstruation onset, and treatment group found that the treatment group was the only factor associated with hyperandrogenism with oligomenorrhea, with a relative risk of 2.04 (95% CI 1-4.16, P=0.07) for women with untreated precocious puberty.
Untreated CPP women more often underwent ovulation induction or in vitro fertilization than treated women and controls.
Logistic regression analysis among CPP women with variables including age at puberty onset and menarche, duration of puberty, current age, hyperandrogenism with oligomenorrhea, and treatment group again found that treatment group was the only factor consistently associated with fertility problems, with an odds ratio of 3.40 (95% CI 1.15-10, P=0.047) for those who were untreated.
Pregnancies were normal in 90% of the CPP women and in 91% of controls, and complications didn't differ between the groups.
The finding that education level, marital status, and number of children were similar for women with CPP compared with those who'd had normal puberty was "reassuring," the researchers observed.
included early initiation into sex and motherhood and high rates of school dropout, they noted.
But the findings of this study suggest that the behavioral and psychological difficulties associated with CPP during adolescence largely resolve by early adulthood, they noted.
Nonetheless, the higher rates of hyperandrogenism suggest that the underlying neuroendocrine abnormality that prompts precocious puberty persists through adulthood.
"Continued follow-up of former CPP women is warranted to determine whether CPP will have long-term implications on the general health status in this population, and increased risk for premature ovarian failure and premature menopause in late reproductive years," Lazar and colleagues concluded.
Limitations of this analysis included small numbers in the CyA group and a lack of information on psychological and quality-of-life measures.
Disclosures
The study was supported by the Clalit Research Institute.
The authors reported no financial disclosures.
Primary Source
Clinical Endocrinology
Lazar L, et al "Treated and untreated women with idiopathic precocious puberty: long-term follow-up and reproductive outcome between the third and fifth decades" Clin Endocrinol 2013; DOI: 10.1111/cen.12319.