LMP299Y1 Lecture Notes - Lecture 10: Hypergonadotropic Hypogonadism, Hypogonadotropic Hypogonadism, Secondary Sex Characteristic

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Published on 12 Apr 2013
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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)
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 Gonadotrophins
Testicular failure Hypogonadotrophic
Hyperprolactinemia
Different enzymes
convert
testosterone into
different products
This is important in the
conversion of
testosterone to
estradiol (estrogen)
(DHT)
FSH and LH (since
there is lack of
feedback)
Pituitary tumor
may be producing
larger amounts of
prolactin
Primary hypogonadism hypogonadism
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 massive increase in LH release to produce ovulation at mid-cycle
o Selective monotonic elevation of FSH in the late luteal to early follicular stages; FSH rise initiates the next wave
of follicular maturation (next cycle).
EVALUATION OF OVULATION
Progesterone measurement (if it is increased then there is ovulation)
- beginning rise immediately after ovulation
- Peak within 5 to 9 d during the mid-luteal phase (days 21-23)
- If pregnant, hCG stimulates corpus luteum, progesterone rise continues
Basal body temperature
- Biphasic if ovulation occurring
This is either pituitary or hypothalamus defect
Hormones form the hypothalamus are released in pulses
If there is no pregnancy
then the progesterone
decreases
Progesterone increase after
ovulation released by the
corpus luteum
The red line
shows the
estrogen