PATHOPHISIOLOGY OF SEX HORMONES R. Mohammadi Biochemist (Ph.D.) Faculty member of Medical Faculty
CHOLESTEROL IS THE PRECURSOR OF STERIOD HORMONES
Cholesterol Pregnenolone 17-OH 17βHSD Pregnenolne DHEA Andrstendiol 17 α- Hydroxylase 17-20 Lyase 3βHSD Δ 4,5 Isomerase 3βHSD Δ 4,5 Isomerase 3βHSD Δ 4,5 Isomerase 3βHSD Δ 4,5 Isomerase Progestrone 17 α- Hydroxylase 17-20 Lyase 17βHSD 17-OH Progestrone Androstendione Testosterone 21 - Hydroxylase 21 - Hydroxylase Aromatase Aromatase 11-Deoxy Corticosterone 11β - Hydroxylase 11-Deoxy Cortisol 11β - Hydroxylase Estrone 16 α- Hd Hydroxylase 17βHSD Estradiol 16 α- Hd Hydroxylase Corticosterone 17βHSD Cortisol 16-OH Estrone Esterone Aldosterone Synthase Aldoesterone
PROTEIN CARRIERS OF STEROID HORMONES CORTICOSTEROID BINDING GLOBULIN (CBG) SEX HORMONE BINDING GLOBULIN (SHBG) ALBUMIN (Alb)
Progesteron Synthesis
Cholesterol 20-22 Lyase Pregnenolone 3βHSDβ Δ 4,5 Isomerase Progestrone 21 - Hydroxylase 11-Deoxy Corticosterone 11β - Hydroxylase y Corticosterone Aldosterone Synthase Aldoesterone
Cholesterol 20-22 Lyase Pregnenolone Progestrone 17 α- Hydroxylase 3βHSD Δ 4,5 Isomerase 17 α- Hydroxylase 17-OH Pregnenolne 17-OH Progestrone 3βHSD Δ 4,5 Isomerase 21 - Hydroxylase 11-Deoxy Cortisol 11β - Hydroxylase Cortisol
Cholesterol Pregnenolone 17-OH Pregnenolne 17 α- Hydroxylase 17-20 Lyase DHEA 17βHSD Andrstendiol 3βHSD Δ 4,5 Isomerase 3βHSD Δ 4,5 Isomerase 3βHSD Δ 4,5 Isomerase 3βHSD Δ 4,5 Isomerase Progestrone 17 α- Hydroxylase 17-20 Lyase 17βHSD 17-OH Progestrone Androstendione Testosterone Aromatase Estrone
Cholesterol Pregnenolone 17-OH Pregnenolne 17 α- Hydroxylase 17-20 Lyase DHEA 17βHSD Andrstendiol 3βHSD Δ 4,5 Isomerase 3βHSD Δ 4,5 Isomerase 3βHSD Δ 4,5 Isomerase 3βHSD Δ 4,5 Isomerase Progestrone 17 α- Hydroxylase 17-20 Lyase 17-OH Progestrone Androstendione 17βHSD Testosterone Aromatase Aromatase Estrone Estradiol
TESTOSTERONE IN BLOOD Free Testoesterone (2-3%) Albumin-bound bound Testoesterone t (33 33-50 50%) SHBG-bound Testoesterone (44-65%)
MALE HYPOGONADISM Hypogonadotropic Hypogonadism Hypergonadotropic Hypogonadism Abnormality Androgen Function
CENTRAL HYPOGONADISM Hpothalamic dysfunction (Kallmann s syndrome) Pituitary failure (Tumor, radiation, surgery) Hyperprolactinemia Exogenous androgens Thyroid disorders
PRIMARY HYPOGONADISM Chromosomal abnormailties Enzyme Deficiecy Acquired (Infection, Drugs, Radiation)
LABORATORY APPROACH TO MALE HYPOGONADISM According Sperm Analysis Serum LH, FSH, and Testoesterone
Oligo- or Azoospermia Low Testosterone, High LH and FSH Primary Hypogonadism Chromosomal analysis
Oligo- or Azoospermia Low Testosterone, Normal or Low LH and FSH Central Hypogonadism Pituitary-hypothalamic evaluation Serum PRL CG stimulation test
Oligo- or Azoospermia Normal Testosterone, LH and FSH Congenital absence of vas deferens and seminal vesicles Ductal obstruction Spermatogenic Failure Seminal Fluid Fructose Testicular Biopsy
Oligospermia Normal Testosterone and LH, High FSH Seminiferous Tubule Failure
Oligo- or Azoospermia High Testosterone and LH, Normal FSH Hyperthyroidism Partial androgen insensitivity Serum TSH
ESTRADIOL IN BLOOD Free Estradiol (3%) Albumin-bound bound Estradiol (37 37-57 57%) SHBG-bound Estradiol (40 40-60%)
FEMALE ABNORMALITIES Hirsutism and Virilization Amenorrhea Menopause
FIVE STEPS IN AMENORRHEA EVALUATION STEP 1 : Serum > 5 miu/ml Pregnancy Trophoblastic disease hcg secreting tumor Serum hcg Measuring
FIVE STEPS IN AMENORRHEA EVALUATION STEP 2 : Serum PRL, Serum PRL, TSH, FT4 High PRL Normal TSH and FT4 Evaluation of Hyperprolactinemia Normal or High PRL Abnormal TSH and FT4 Evaluation of Thyroid Disease
FIVE STEPS IN AMENORRHEA EVALUATION STEP 3 : Progestin Withdrawal Test Bleeding Absent Anatomical Abnormalities Hypogonadism Bleeding Present PCOS Ovarian tumor Adrenal Tumor Adrenal Hyperplasia
FIVE STEPS IN AMENORRHEA EVALUATION STEP 4 : serum FSH and LH High Primary Ovarian Failure Low or Normal Hypothalamic Pituitary Disease
FIVE STEPS IN AMENORRHEA EVALUATION STEP 5 : Serrum Serrum Androgens High Testosterone PCOS Ovarian tumor High DHEAS Adrenal Tumor High 17-OH Progestrone Adrenal Hyperplasia
ACTUAL MENOPAUSE Is defined as permanent cessation of menstruation resulting from loss of ovarian follicular activity E2 and progesterone decrease, and FSH and LH increase High LH result in androgen excess
PERIMENOPAUSE Is the transition phase which can last from 2 to 8 years FSH increases and E2 decreases, but LH and progesteron are normal Short follicular l phase with premature ovulation High FSH may be due to decrease in inhibin