Sex Hormones. Although Sex Hormones contribute to the major differences between males and females, their endocrine axis follows the same basic principles.
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Slide 1
Sex Hormones
Slide 2
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.
Slide 3
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 !
Slide 4
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.
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
Slide 8
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
Slide 9
Slide 10
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
Slide 11
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
Slide 12
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
Slide 13
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)
Slide 14
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)
Slide 15
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
Slide 16
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
Slide 17
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
Slide 18
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
Slide 19
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
Slide 20
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
Slide 21
Different mechanisms for hyperprolactinemia Prolactinoma
Macroadenoma: functioning secreting tumours Diameter>10mm,
PRL>200ng/ml Direct Secretion Microadenoma : non functioning,
non secreting tumours Diameter