Introduction:
Puberty is a normal physiological process that a child’s body undergoes. The process may be delayed or absent in certain children and lead to a condition known as delayed puberty. Delays in puberty can cause multiple health problems, from lack of sexual development and infertility to psychological distress in a child. Different reasons can lead to delayed puberty, like constitutional and physiological delay, hypogonadism (improper functioning of testes in men and ovaries in women), malnutrition, long-standing diseases, cancer, etc. Therapeutic induction of puberty depends primarily on the cause of the delay.
What Is Puberty?
Puberty is a series of physical changes through which a child’s body matures into an adult and becomes capable of sexual reproduction. Puberty is a growth spurt stimulated by multiple hormones like a gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). The onset of puberty requires proper functioning of the hypothalamic-pituitary-gonadal axis, which is the combined functioning of the hypothalamus, pituitary gland, and gonads to regulate reproductive functioning and immunity in an individual. The hypothalamus begins secretion of the gonadotropin-releasing hormone. The pituitary gland responds to this by secreting gonadotropin hormones which in turn stimulate the growth of testes in boys and ovaries in girls. The hormones responsible for the onset of puberty are in a state of dormancy or inactivity during childhood.
What Is Delayed Puberty?
When a child (teen) passes this expected age range of puberty without showing any physical changes or sexual maturation, then this condition is referred to as delayed puberty. This individual will either entirely lack or will have incomplete development of secondary sexual characteristics such as breast development, alteration in voice pitch, growth of facial hair, etc. Delayed puberty usually starts later than 13 years in girls and 14 years in boys (this delay can be of several years). It affects approximately two percent of the total adolescent population. Delayed puberty is also known as constitutional delay of growth and puberty.
What Causes Delayed Puberty?
There is no one specific cause of delayed puberty, but it can occur as a result of several factors. The multiple causes of delayed puberty include:
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Constitutional and Physiologic Delay: It is the most common cause of delayed puberty in which a healthy child has a slower rate of development and growth than the average child. These individuals are referred to as “late bloomers.” Although the growth spurts and the sexual maturation is delayed, it eventually proceeds normally. A constitutional delay is the most common cause of delayed puberty; in females, almost 30 %, and in males, almost 65 % experience constitutional delay of puberty. The constitutional delay of puberty is usually inherited.
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Malnutrition or Chronic Disease: Malnutrition and chronic diseases can cause a temporary and reversible delay in puberty. Chronic diseases that can cause delayed puberty include; sickle cell anemia, thalassemia, cystic fibrosis, HIV or AIDS (human immunodeficiency virus or acquired immunodeficiency syndrome), hypothyroidism, kidney problems, celiac diseases, bowel diseases, uncontrolled diabetes mellitus, etc. Children who are cancer survivors also have delayed puberty because of their cancer treatment. Individuals who are malnourished or have eating disorders will also have delayed puberty due to undernutrition.
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Primary Failure of Ovaries and Testes: The sexual maturation in an individual takes place when the hypothalamus begins secretion of the gonadotropin-releasing hormone. The pituitary gland responds to this by secreting gonadotropin hormones which in turn stimulate the growth of testes in boys and ovaries in girls. This whole cycle is known as the HPG axis (hypothalamic-pituitary-gonadal axis). Primary failure of the ovaries and testes occurs due to a lack of hormonal response by the final receptor of the HPG axis. This failure in response eventually causes delayed puberty, and it can be due to congenital or acquired diseases like Turner syndrome, Noonan syndrome, gonadal dysgenesis, mumps, trauma, irradiation, etc.
How Is Puberty Induced in Constitutional Delay of Growth and Puberty?
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Constitutional delay of growth and puberty (CDGP) is typically treated by keeping a close eye on the symptoms of the patient along with induction of puberty with the help of low-dose testosterone in boys and estrogen in girls.
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CDGP is often associated with short stature, and the use of growth hormone replacement therapy is useful in increasing height.
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In boys affected by CDGP, another approach for inducing puberty is stopping the production of estrogen (with the help of aromatase inhibitors). It is also helpful in increasing the height.
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For girls affected by CDGP, oral and transdermal estradiol replacements are given.
Drugs used for the treatment of CDGP are as follows:
How Is Puberty Induced in Hypogonadotropic Hypogonadism?
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In boys and girls affected by hypogonadotropic hypogonadism or HH (Hypogonadotropic hypogonadism is a type of hypogonadism occurring due to pituitary or hypothalamic disorder), the initial treatment modalities are the same as that of CDGP. However, the doses are slowly and gradually increased into full adult replacement over three years.
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Both sexes require treatment with gonadotropin hormone replacement therapy to induce fertility.
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In teenage boys, monotherapy with human chorionic gonadotropin (hCG) or combination therapy with hCG and the recombinant follicle-stimulating hormone is found to be useful in the growth of the testes and inducing fertility.
What Are the Side Effects of Therapies Used to Induce Puberty?
The various side effects of different medications and therapies used for inducing puberty are:
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Increased number of red blood cells (RBCs).
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Weight gain.
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Excessive enlargement of the prostate gland.
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High doses of testosterone replacement therapy can cause early closure of the epiphyseal plate, which marks the end of growth in a particular bone.
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All intramuscular injections can cause pain, swelling, redness, allergic reactions, abscess, etc.
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Patches and gels can cause local irritation on the skin.
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Estradiol replacement therapy can cause liver damage, increase the risk of thromboembolism (obstruction of blood vessels by blood clots), and increase blood pressure in the arteries.
Conclusion:
Various hormone replacement therapies and drugs have been useful in inducing puberty in boys and girls. However, there is still a lot of research going on in this field, and there are a lot of areas of uncertainty regarding the effectiveness of certain treatment modalities. Apart from the physical problems, delay or lack of puberty causes a lot of psychological stress on the affected child. This is again a matter of concern, and the treatment for inducing puberty should be combined with psychological therapy. Various newer therapies for inducing puberty are being proposed, but their effectiveness and side effects are still unknown.
