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University of Toronto St. George
Laboratory Medicine and Pathobiology

LECTURE TEN: INFERTILITY INFERTILITY  Definition: failure to conceive after one year of regular, unprotected intercourse.  Causes of infertility: - Male factors, 40% * NOTE: assessment of male is equally important as female - Female factors, 50% - Unknown, 10%  In female, endocrine abnormalities are found in 1/3 of cases * Hormone dysfunction is a rare cause of male infertility. SEX STEROID HORMONES  Sources: Gonads (testis and ovary) and peripheral conversion (adrenal & adipose tissues)  Testosterone and androgens *in women, 1/2 from ovary & 1/2 from peripheral conversion of dehydroepiandrosterone (DHEA) and DHEA-Sulphate (DHEAS) secreted by adrenal cortex. * DHEAS, marker in differential diagnosis of the source of excessive androgen production in women  Estradiol and estrogens *In normal male, estradiol present in low concentrations.  Sex hormone-binding globulin (SHBG) - Higher affinity for testosterone than for estradiol - Estradiol stimulates SHBG synthesis in liver; testosterone decreases it. - The plasma concentration of SHBG in females is twice that in males - Factors which alter SHBG concentration alter the ratio of unbound testosterone to unbound estradiol. CONTROL OF TESTICULAR FUNCTION - Negative feedback by the testosterone - This hormone is more potent than testosterone (it is made from testosterone) and it is important in male genital formation and also in puberty (male sexual features and secondary sexual characteristics) DISORDERS OF MALE SEX HORMONES  Hypogonadism: Primary: hypergonadotropic hypogonadism – testicular failure - Congenital defects - Acquired defects Secondary and tertiary: hypogonadotropic hypogonadism - Pituitary tumors - Hypothalamic disorders, e.g. Kallmann’s syndrome (GnRH def.) * GnRH stimulation test – for investigation of the causes  Defects in androgen action – sexual differentiation - Testicular feminization syndrome (Androgen Insensitivity Syndrome – due to androgen receptor def.) - 5α-reductase deficiency (DHT deficiency, only affect chromosomal 46XY males) This is important in the conversion of testosterone to estradiol (estrogen) Different enzymes convert testosterone into different products (DHT) INVESTIGATION OF INFERTILITY IN MEN History and examination Spermanalysis No further endocrine test Normal Abnormal Measure testoste rone, FSH, LH, prolacti n Testosterone Testosterone Prolactin Gonadotrophins FSH and LH (since Gonadotrophins there is lack of Pituitary tumor feedback) may be producing Testicular failure Hypogonadotrophic larger amounts of Hyperprolactinemia prolactin Primary hypogonadism hypogonadism This is either pituitary or hypothalamus defect Hormones form the hypothalamus are released in pulses Fast pulse favours the LH LH PEAK: induced by the estrogen peak Progesterone increase after ovulation – released by the corpus luteum If there is no pregnancy The red line then the progesterone shows the decreases estrogen NORMAL MENSTRUAL CYCLE THE BASICS o Selective secretion of FSH and LH during ovulatory cycles reflects changing GnRH pulse stimuli o Slow frequency pulses favor FSH; more rapid pulses favor LH. o Selective inhibitory feedback of estradiol and inhibin on FSH release, plus positive actions of ovarian steroids on LH, combine to produce the two essential features of an ovulatory cycle o A m
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