Delayed PubertyTopics in Adolescent Gynecology

Michael Wolfe, M.D.University of Kansas School of Medicine

Department of Obstetrics and Gynecology

Objectives

Review normal pubertal development Discuss common etiologies of delayed

puberty Discuss evaluation and management of

primary amenorrhea

Normal Puberty

ThelarcheAdrenarcheGrowth SpurtMenarche

Tanner Staging – Breast Development

Tanner Staging – Pubic Hair

Prepubertal Period

3 changes in the low endocrine state of childhood occur Adrenarche Decreased repression of the “gonadostat” Gradual amplification of peptide-peptide

and peptide-steroid interactions leading to gonadarche

What is delayed puberty?

Defined clinically as the absence or incomplete development of secondary sexual characteristics by an age at which 95% of children of that sex and culture have initiated sexual maturation

In the U.S. the National Center for Health Statistics states that the upper 95% for females is age 12, with breast development being the first sign

Etiologies

Hypergonadotropic Hypogonadism (43%) Ovarian failure with normal or abnormal karyotype

Hypogonadotropic Hypogonadism (31%) Reversible vs. irreversible

Eugonadism (26%) Anatomic abnormalities of the target organ or

outflow tract

Hypergonadotropic Hypogonadism

Postmenopausal levels of FSH and LH Gonadal Dysgenesis

45X 46XX 46XY

Mosaicism

Hypogonadotropic HypogonadismReversible

Physiologic delay / Functional Hypothalamic Amenorrhea

Weight loss/anorexia Primary hypothyroidism Prolactinoma Congenital adrenal hyperplasia Cushing’s syndrome

Hypogonadotropic HypogonadismIrreversible

GnRH deficiency Hypopituitarism, pituitary adenomas,

malignant pituitary tumors Craniopharyngioma Congenital CNS defects

Eugonadism

Mullerian Agenesis Vaginal Septum Imperforate Hymen Androgen Insensitivity Syndrome

Review

Classification by gonadotropin levels Hypergonadotropic hypogonadism Hypogonadotropic hypogonadism Eugonadism

Disorders by compartment Compartment 1: Uterus, outflow tract Compartment 2: Ovary Compartment 3: Anterior Pituitary Compartment 4: CNS, Hypothalamus

Evaluation

History Physical Exam Imaging Studies

Initial Labs

Uterus Absent Karyotype Serum testosterone

Uterus Present TSH, Prolactin, Progestational Challenge FSH, LH, estradiol Other labs

Progestational Challenge

Positive withdrawal bleeding Suggests intact outflow tract Likely due to anovulation Functional ovary, pituitary, and CNS is confirmed

Negative withdrawal bleeding Administer hormonal cycle of estrogen with

progestational agent May skip this step if certain of normal uterus

Evaluation after estrogen/progesterone

Measure gonadotropin levels (FSH and LH) Elevated Gonadotropins Normal Gonadotropins Low Gonadotropins

Gonadotropin Levels

Elevated gonadotropins Normal gonadotropins Low gonadotropins

Treatment Strategies

Correct underlying pathology Prevent complications of disease

process Sex steroids

Summary

Normal Puberty Delayed Puberty

Hypergonadotropic Hypogonadism (elevated FSH, LH)

Hypogonadotropic Hypogonadism (low FSH, LH) Eugonadism

History and Physical Exam Work-up: TSH, Prolactin, Progestational

Challenge, Estrogen/Progesterone cycle, gonadotropin assays, imaging studies

Resources

Clinical Gynecologic Endocrinology and Infertility.6th ed. Speroff, Leon, et al. Lippincott Williams and Wilkins, 1999.

UpToDate, 2004