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Sex Hormones

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Although Sex Hormones contribute to the major differences between males and females, their endocrine axis follows the same basic principles. Therefore the male and female reproductive axes can be more easily understood when considered as one system with certain differences rather than two different ones.

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Hypothalamic factor : GnRH The first step in sex hormone formation is the release of the Gonadotropin Releasing Hormone from the hypothalamus GnRH is released in a PULSATILE fashion Rate of GnRH pulse affects subsequent FSH/LH release pattern Continuous administration of GnRH Decreases FSH/LH !

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Pituitary factors : Gonadotropins The anterior pituitary responds to GnRH by secreting gonadotropins: FSH= Follicular Stimulating Hormone LH = Luteinizing Hormone Although the effects of FSH and LH are quite different in males and females, a certain analogy exists : Gonadotropins act via two-cell system in males and females.

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Males LH FSH Leydig Sertoli cells cells Testosterone Spermatogenesis synthesis

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Females

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LH Theca Cells Androgen Synthesis FSH Granulosa Cells Aromatase Activation Estrogen Note: All Estrogen is synthesised from androgen precursors via aromatase enzyme Progesterone is first synthesised then converted to androgen precursors in theca and granulosa cells under the effect of LH

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Negative Feedback Testosterone inhibits Hypothalamic GnRH and pituitary FSH/LH secretion Estrogen: FSH/ LH, May also GnRH Estrogen + Progesterone: estrogen effect multiplied Progesterone alone may GnRH pulse frequency Anterior pituitary responsiveness to GnRH

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Physiologic functions : Testosterone Testosterone is essentially a prohormone with modest androgenic activity! Must first be converted to the more potent dihydrotestosterone via enzyme 5 reductase Fetal effects: Development of male reproductive organs/ Suppression of female ones Descent of Testes in scrotum

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At Puberty: Increased size and development of reproductive organs Development of secondary sexual characteristics: Body Hair distribution (Baldness?) Male Voice Increased skin thickness and sebaceous gland secretions (Acne?) Metabolic effects: Anabolic : increases protein and muscle formation (50% > women) Bones: epiphyseal bone growth acceleration growth spurt and epiphyseal closure. Also increased thickness of bones and Ca deposition. BMR and Erythropoeisis Na/ water reabsorption Behavioural effects: Aggressiveness and better spatial functions

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Androgens and derivatives UsesAdverse effects Replacement in hypogonadism Osteoporosis Catabolic and wasting states Refractory anaemias All androgens suppress gonadotropin secretion Some can cause gyneacomastia Some can cause hepatotoxicity Some can LDL and HDL Some may impair glucose tolerance Virilisation in females

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Physiologic functions : Estrogen Development of uterus, vagina, fallopian tubes and breast Increases tubal contractility (enhancing ovum transport to uterus) Increases watery content of cervical mucus to facilitate sperm penetration Development of secondary sexual characteristics: Axillary and pubic hair growth Nipple pigmentation Metabolic effects: Bones: bone mass and epiphyseal growth growth spurt & epiphyseal closure Proteins: slight in protein deposition Fats: deposition in characteristic female areas (eg: buttocks and breasts) BMR: (lower than males) Na/ water reabsorption : slight, but in pregnancy ( estrogen from placenta)

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Lipid metabolism HDL, LDL May inhibit oxidation of LDL Vasodilation Retardation of atherogenesis Clotting : o production of clotting factors II, VII, IX, X, and XII o anticoagulation factors (Protein C, Protein S and Antithrombin III)

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Estrogens and derivatives Uses Component of combined contraceptives Hormone replacement therapy (HRT) in hypogonadism and post menopausal women Adverse effects Risk of endometrial, cervical and vaginal cancer Edema and reduced glucose tolerance Risk of Thromboembolism [Short term use: increased blood coagulability] Long term use : hepatic dysfunction : clotting factors and coagulability Feminization in males

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Physiologic effects: Progestins Reproductive tract: (maintenance of Pregnancy) Decreases estrogen mediated endometrial proliferation Secretory functions of uterus Uterine contraction Rate of oocyte transport through oviduct Thickening of cervical mucus and decreased sperm penetration Metabolic effects: LDL CNS effects: Basal body temperature, with ovulation

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Progestins and derivatives UsesAdverse effects Contraception (alone and with Estrogen) Emergency contraception HRT Prevention of Estrogen mediated endometrial hyperplasia Diagnostically in 2ry amenorrhea (Provera challenge) May impair glucose tolerance Counteract the beneficial effects of Estrogen on lipid profile

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Pathophysiology of reproductive disorders Disruption of H-P- Gonadal axis PCOS (Polycystic ovary syndrome) Prolactinoma* Inappropriate growth of hormone dependent tissues Breast Cancer E/P/PRL dependent Prostatic hyperplasia/cancer (Androgen dependent) Deficiency of gonadal hormones Primary Hypogonadism (e.g: Premature Ovarian failure) Menopause * Bromocriptine Carbegoline Inhibitors of gonadal hormones Replacement hormones

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Hyperprolactinemia & fertility Prolactin is secreted from lactotrophs in anterior pituitary gland However unlike the rest of anterior pituitary hormones, prolactin secretion is under tonic INHIBITION by Dopamine from hypothalamus Decreased or interrupted dopamine supply Increased Prolactin secretion

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Lab values: PRL, FSH, LH, Estrogen and Progesterone Treatment : Dopamine analogues 1.Carbegoline 2.Bromocriptine Prolactin GnRH Pituitary sensitivity to GnRH Gonadotropins and Sex Hormones 1.Infertility 2.Erectile dysfunction 3.Gynecomastia 1.Anovulatory infertility 2.Oligorrhea/ Amenorrhea 3.Galactorrhea 4. Double vision(?) 5. Headaches

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Different mechanisms for hyperprolactinemia Prolactinoma Macroadenoma: functioning secreting tumours Diameter>10mm, PRL>200ng/ml Direct Secretion Microadenoma : non functioning, non secreting tumours Diameter