Delayed puberty natural history, complications and prognosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

The symptoms of puberty usually develop between ages 8 to 13 in girls and 9 to 14 in boys and start with breast development in girls and testicular enlargement in boys. If the testicular enlargement or breast development has not occurred at a mean age of puberty in population plus 2-2.5 standard deviation (SD), it will be called delayed puberty. The mean age depends on various factors, such as race, nutrition, and also socioeconomic status. Recently, the age of onset of puberty is decreasing in the US and other countries. The main complications of delayed puberty are osteoporosis, psychological problems, polycythemia, and irritation from hormonal gels and patches. The major determinant of delayed puberty prognosis is underlying co-morbidity, not the disease itself. Constitutional delay of growth and puberty (CDGP) has an excellent prognosis. The puberty and final height in these patients will be normal in the future, without any hormone replacement therapy.

• The symptoms of puberty usually develop between ages 8 to 13 in girls and ages 9 to 14 in boys and start with breast development in girls and testicular enlargement in boys.
• If the testicular enlargement or breast development has not occurred at a mean age of puberty in population plus 2-2.5 SD, it will be called delayed puberty. The mean age depends on various factors, such as race, nutrition, and also socioeconomic status. Recently, the age of onset of puberty is decreasing in the US and other countries.
• If left untreated, all of the patients with a constitutional delay of puberty and growth may progress to develop normal puberty and growth.
• All patients with delayed puberty have to be precisely monitored until normal puberty and growth become accomplished. It may take about 2-5 years. Final height can be measured by adding or subtracting 2.5 inches to the average height of parents. On average, puberty is accompanied by gaining 25 cm of height in girls and 30 cm in boys.

Delayed puberty in boys is identified as:^[1]

• No sign of testicular enlargement by 14 years of the age

OR

• No pubic hair by 15 years of age

OR

• No penis and testicles development to adult type 5 years after onset of puberty

Delayed puberty in girls is identified as:^[1]

• No signs of breast development by 14 years of age

OR

• No pubic hair by 14 years of age

OR

• No breast development to adult type 5 years after onset of puberty

OR

• No menstruation by 16 years of age

Approximate mean ages for onset of various pubertal changes are as follows:

Developmental changes during puberty in girls occur over a period of 3-5 years, usually between 9 and 14 years of age. They include the occurrence of secondary sex characteristics beginning with breast development, the adolescent growth spurt, the onset of menarche (not correspond to the end of puberty), and the acquisition of fertility, as well as profound psychological modifications.^[2]

• Thelarche: 10 years and 5 months of age
• Pubarche: 11 years of age
• Growth spurt: 10-12.5 years of age
• Menarche: 12.5 years of age
• Adult height reached: 14.5 years of age

• Testicular enlargement: 11.5 years of age
• Pubic hair: 12 years of age
• Growth spurt: 12.5–15 years of age
• Completion of growth: 17.5 years of age

Osteoporosis

• Lack of estrogen and other sex steroids can lead to decreasing bone mineralization and osteoporosis.^[3]
• The amount of bone mass gained during puberty is the key determinant factor in development of osteoporosis.^[3]
• If left untreated, patients with delayed puberty attain normal sexual maturation but will experience a decreased peak bone mass .^[4]

Psychological problems^[5]

• Delayed puberty may threaten the final height and also adult phenotype.
• Delayed or absent secondary sexual characteristics may affect a person’s self-esteem and interpersonal relationships.
• Patients with a disease resulting in anorchia have to be counseled about testicular prosthesis.

Polycythemia

• The use of testosterone in the treatment of delayed puberty can cause RBCs overproduction which can lead to increased hematocrit.

Irritation from gels and patches

• Therapeutic hormonal gels and patches that are frequently used in delayed puberty can cause allergic reactions and irritation.

• The major determinant of prognosis in delayed puberty is underlying co-morbidity, not the disease itself.
• Constitutional delay of growth and puberty (CDGP) has an excellent prognosis. The puberty and final height in these patients will occur normally in the future even without any hormone replacement therapy.
• Patients with benign co-morbidity induced delayed puberty, like delayed puberty due to lifestyle disorders (malnutrition or excessive exercise) or mild chronic diseases, can completely gain their normal puberty characteristics after suitable treatment of underlying diseases.
• Permanent causes of delayed puberty, such as idiopathic hypogonadotropic hypogonadism, genetic diseases, chromosomal disorders (e.g., Turner’s syndrome or Klinefelter’s syndrome), or pituitary surgical procedures (e.g., craniopharyngioma treatment) need lifelong hormone replacement therapy.^[6]

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