Puberty

Definition of puberty It is the physiological stage that leads to reproductive capability manifested by spermatogenesis in the male and ovulation in the female.

Conditions influence the age onset of puberty Socioeconomic conditions Nutritional status States of health Chronic disease Altitudes Genetic factors Strenuous physical activity

Female secondary sex characteristics Breast enlargement the first sign of puberty in % 85 girls Pubic hair Axillary hair Vagina and uterus Menarche (stage 4), mean age 12.8 years

Male secondary sex characteristics External genitalia Pubic hair Axillary and facial hair Voice change Spermarche

Changes in body size and shape 1. Stature: PVH F stage III M stage IV 2. Bone age 3. Body composition 4. Body build proportions 5. Strength

Precocious puberty Appearance of any sign of secondary sexual maturation at an age more than 2SD below the mean. The age of 7y in girls and 9y in boys

Precocious puberty True P. puberty Pseudo P. puberty Contrasexual precocity

True precocious puberty Idiopathic true precocious puberty CNS tumors Other CNS disorders After late treatment of C.A.H. or previous chronic exposure to gonadal steroids

Idiopathic precocious puberty Most often sporadic, rarely A.R. Is more common in girls Progression of secondary sexual maturation is often more rapid than normal puberty There is increased risk for the development of Ca. of breast in adulthhood Ht. velocity, somatic development, skeletal maturation are increased .

Treatment of true P.P Medroxyprogesterone acetate Cyproterone acetate The drug of choice is LHRH agonists

Objectives of the managements and treatment of T.P.P Detection and treatment of an expanding intracranial lesion Arrest of premature sexual maturation Regression of secondary sexual characteristics Attainment of normal mature height Reduction of risk of sexual abuse Prevention of pregnancy in girls Preservation of future fertility Diminish the increased risk of breast cancer

Action of LHRH agonists in TPP A selective highly specific Pharmacological clamp on the secretion of gonadotropin Chronic administration induces desensitization of the pituitary gonadotrope to the action of endogenous LHRH. As a consequence: Inhibition of pulsatile secretion of LH and FSH Inhibition of gonadotropin secretion

Indications for therapy with LHRH agonists in T.P.P In children with endocrine features of T.P.P Rapid advancement over a period of 6 mo to 1 y A serum testosterone concentration > 1ng/mL in boys less than 8 y of age Onset of menarche in girls less than 9 y of age

Side effect of LHRH agonists Erythema (most common), sterile abscess and hematoma at the site of injection Anaphylactic reaction (rare) Asthma attack (nasal route) Bone demineralization in girls Antibody formation Acceleration of sexual precocity Diarrhea, constipation

Pseudo-precocious puberty (In boys) Gonadotropin – secreting tumors Inside CNS Outside CNS 2. Increase androgen secretion by adrenal or testis C.A.H. Virilizing adrenal tumor Leydig cell adenoma Familial testotoxicosis

Pseudo-precocious puberty (In girls) Estrogen – secreting ovarian or adrenal neoplasm Ovarian cyst Peutz – jeghers synd.

Pseudo – precocious puberty (In both sexes) McCune – Albright synd. Hypothyroidism Iatrogenic or exogenous

McCune – Albright synd. Café au – lait spots Polystotic fibrous dysplasia Endocrine hyperfunction

Contrasexual precocity Feminization in boys and virilization in girls

Feminization in males Adrenal neoplasm Chorioepithelioma 11-β hydroxylase def. Late-onset C.A.H. Testicular neoplasm (peutz-jeghers synd.) ↑Extraglandular conversion adrenal androgens to estrogen Iatrogenic (exposure to estroges)

Virilization in girls C.A.H. (21-, 11-, 3  HSD def.) Virilizing adrenal neoplasm Virilizing ovarian neoplasm Iatrogenic (exposure to androgens)

Variation of pubertal development Premature thelarche Premature adrenarche Premature menarche Adolescent gynecomastia in boys

Classification of delayed puberty Idiopathic Hypogonadothropic hypogonadism Hypergonadothropic hypogonadism

Hypogonadoropic hypogonadism CNS disorders Tumors Congenital malformations Radiation therapy Head trauma Other causes

Classification of delayed puberty Isolated gonadotropin deficiency Kallmann syndrome with hyposmia or anosmia Congenital adrenal hypoplasia Other disorders Idiopathic and genetic forms of multiple pituitary Hormone deficiencies Miscellaneous disorders Prader-willi syndrome Laurence-moon-biedl syndrome

Characteristics of isolated gonadotropin deficiency Males more commonly affected Familial or sporadic Height normal Eunuchoid skeletal proportions Delayed bone age Small testes: diameter ≤ 2.5 cm Normal adrenarche Examine for anosmia or hyposmia (kallmann syndrome) Look for associated malformations (facial, skeletal, renal)

Features of Kallmann syndrome Clinical LHRH deficiency: absent or arrested puberty Anosmia or hyposmia In infancy: microphallus, cryptorchidism Normal stature and growth in childhood Normal adrenarche Eunuchoid proportions Associated midline defects MRI: aplasia or hypoplasia of olfactory bulbs Cont.

Features of Kallmann syndrome Prevalence: approximately 1 in 7500 males, 1 in 50000 females Inheritance: sporadic and familial cases; genetic heterogeneity X linked X-linkes recessive X chromosome deletion: Xp22.3 Autosomal (Dominat, recessive) Anatomy: developmental field defect Aplasia or hypoplasia of olfactory bulb

Classification of delayed puberty Functional gonadotropin deficiency Chronic systemic disease and malnutrition Hypothyroidism Diabetes mellitus Cushing disease Hyperprolactinemia Anorexia nervosa Psychogenic amenorrhea Delayed puberty and/or menarche, especially in female athletes and ballet dancers Cont.

Classification of delayed puberty Hypergonadotropic hypogonadims Males Klinefelter syndrome Other forms of primary testicular failure Chemotherapy Radiation therapy LH resistance Testicular biosynthetic defects Anorchia and cryptorchidims Cont.

Classification of delayed puberty Females Turner syndrome 46 XX and 46 XY gonadal dysgenesis Other forms of primary ovarian failure Premature menopause Radiation therapy Chemotherapy Autoimmune oophoritis Polycystic ovary disease Galactosemia

Endocrine diagnosis of constitutional delayed adolescence and hypogonadotropic hypogonadism No single test reliably discriminates between the two diagnoses Onset of puberty in boys is indicated by testes > 2.5 cm in diameter Serum testosterone concentration > 50 ng/dl Pubertal LH response to LHRH bolus Pubertal pattern of LH pulsatility

Endocrine and imaging studies in delayed adolescence Initial assessment Plasma testosterone or estradiol Plasma FSH and LH Plasma thyroxine (and prolaction) Bone age and lateral skull roentgenograph Test of olfaction Cont.

Endocrine and imaging studies in delayed adolescence Follow-up studies Karyotype (short, phenotypic females) MRI and/or CT scan Pelvic sonography (females) LHRH test hCG test (males) Pattern of pulsatile LH secretion Visual acuity and visual fields

Objectives in management and treatment and therapy of delayed adolescence determine site and etiology of abnormality induce and maintain secondary sexual characteristics induce pubertal growth spurt prevent the potential short-term and long-term Psychological, personality and social handicaps of delayed puberty Ensure normal libido and potency Attain fertility Cont.

Therapy of delayed puberty Reassurance and follow-up Repeat evaluation (including serum testosterone or estradiol) in 6 mo Psychosocial handicaps, anxiety, highly concerned: Therapy for 4 mo with Boys: testosterone enanthate 100 mg IM every 4 wk at 14-14.5 y of age. Girls: ethiyl estradiol 5-10 ug daily by mouth or conjugated estrogens 0.3 mg daily by mouth at 13 y of age

Hormonal substitution therapy in boys with hypogonadism Goal: to approximate normal adolescent development when diagnosis is established Initial therapy: at 13 y of age, testosterone enanthate 50 mg IM every month for about 9 mo (6-12 mo) Over the next 3 to 4 y: gradually increase dose to adult replacement dose of 200 mg every 2-3wk Begin replacement therapy in boys with suspected hypogonadotropic hypogonadism by bone age < 14 y To induce fertility at appropriate time: pulsatile LHRH or FSH and hCG therapy

Hormonal substitution therapy in girls with hypogonadism When diagnosis of hypogonadism is firmly established begin hormonal substitution therapy at 12-13y Goal: to approximate normal adolescent development Initial therapy: ethinyl estradiol 5 ug by mouth or conjugated estrogen 0.3 mg (or less) by mount daily for 4-6 mo. After 6 mo of therapy begin cyclic therapy: Estrogen: first 21 d of month Progestogen: 12th to 21st day of month