Hd Hydroxylase. Cholesterol. 17-OH Pregnenolne DHEA Andrstendiol. Pregnenolone. 17-OH Progestrone. Androstendione. Progestrone.

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1 PATHOPHISIOLOGY OF SEX HORMONES R. Mohammadi Biochemist (Ph.D.) Faculty member of Medical Faculty

2 CHOLESTEROL IS THE PRECURSOR OF STERIOD HORMONES

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5 Cholesterol Pregnenolone 17-OH 17βHSD Pregnenolne DHEA Andrstendiol 17 α- Hydroxylase 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 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

6 PROTEIN CARRIERS OF STEROID HORMONES CORTICOSTEROID BINDING GLOBULIN (CBG) SEX HORMONE BINDING GLOBULIN (SHBG) ALBUMIN (Alb)

7 Progesteron Synthesis

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9 Cholesterol Lyase Pregnenolone 3βHSDβ Δ 4,5 Isomerase Progestrone 21 - Hydroxylase 11-Deoxy Corticosterone 11β - Hydroxylase y Corticosterone Aldosterone Synthase Aldoesterone

10 Cholesterol 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

11 Cholesterol Pregnenolone 17-OH Pregnenolne 17 α- Hydroxylase 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 Lyase 17βHSD 17-OH Progestrone Androstendione Testosterone Aromatase Estrone

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14 Cholesterol Pregnenolone 17-OH Pregnenolne 17 α- Hydroxylase 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 Lyase 17-OH Progestrone Androstendione 17βHSD Testosterone Aromatase Aromatase Estrone Estradiol

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19 TESTOSTERONE IN BLOOD Free Testoesterone (2-3%) Albumin-bound bound Testoesterone t ( %) SHBG-bound Testoesterone (44-65%)

20 MALE HYPOGONADISM Hypogonadotropic Hypogonadism Hypergonadotropic Hypogonadism Abnormality Androgen Function

21 CENTRAL HYPOGONADISM Hpothalamic dysfunction (Kallmann s syndrome) Pituitary failure (Tumor, radiation, surgery) Hyperprolactinemia Exogenous androgens Thyroid disorders

22 PRIMARY HYPOGONADISM Chromosomal abnormailties Enzyme Deficiecy Acquired (Infection, Drugs, Radiation)

23 LABORATORY APPROACH TO MALE HYPOGONADISM According Sperm Analysis Serum LH, FSH, and Testoesterone

24 Oligo- or Azoospermia Low Testosterone, High LH and FSH Primary Hypogonadism Chromosomal analysis

25 Oligo- or Azoospermia Low Testosterone, Normal or Low LH and FSH Central Hypogonadism Pituitary-hypothalamic evaluation Serum PRL CG stimulation test

26 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

27 Oligospermia Normal Testosterone and LH, High FSH Seminiferous Tubule Failure

28 Oligo- or Azoospermia High Testosterone and LH, Normal FSH Hyperthyroidism Partial androgen insensitivity Serum TSH

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34 ESTRADIOL IN BLOOD Free Estradiol (3%) Albumin-bound bound Estradiol ( %) SHBG-bound Estradiol ( %)

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38 FEMALE ABNORMALITIES Hirsutism and Virilization Amenorrhea Menopause

39 FIVE STEPS IN AMENORRHEA EVALUATION STEP 1 : Serum > 5 miu/ml Pregnancy Trophoblastic disease hcg secreting tumor Serum hcg Measuring

40 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

41 FIVE STEPS IN AMENORRHEA EVALUATION STEP 3 : Progestin Withdrawal Test Bleeding Absent Anatomical Abnormalities Hypogonadism Bleeding Present PCOS Ovarian tumor Adrenal Tumor Adrenal Hyperplasia

42 FIVE STEPS IN AMENORRHEA EVALUATION STEP 4 : serum FSH and LH High Primary Ovarian Failure Low or Normal Hypothalamic Pituitary Disease

43 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

44 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

45 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

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