Download Lab (12) Sex hormones

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Sex steroid hormones are synthesized in the gonads, adrenal
gland, and placenta.
testosterone, dehydroepiandrosterone
(DHEA),dihydrotestosterone (DHT)
•
: estradiol, estriol, estrone
•
progesterone
•
Generally, “males” tend to have higher androgen
levels, and “females”tend to have higher levels of
estrogens and progestagens.
Dehydroepiandrosterone
The adrenal gland produces DHEA in the early morning hours
and then it declines fairly rapidly throughout the day as it is
quickly cleared by the kidneys.
Small amounts of DHEA are also secreted by the ovaries and
testes
DHEA is a precursor to the production of both testosterone
and the estrogen hormones.
The decline of DHEA is linear with increased age leading
some to regard the DHEA level and a biomarker for aging.
DHEA
Measurement of its level in serum is a useful marker of
adrenal androgen synthesis. Abnormally high levels occur
in several conditions including virilizing adrenal adenoma
and carcinoma , 21 hydroxylase and 3 -B hydroxysteroid
dehydrogenase deficiencies. And some cases of female
hirsutism.
Since very little DHEA is produced by the gonads,
measurement of DHEA may aid in the localization of the
androgen source in virilizing conditions.
Expected values of DHEA
Male 1.8-12.5 ng/ml
Female 1.3-9.8ng/ml
Anti-Mullerian hormone “Ovarian reserve tests”
 Anti-Mullerian Hormone (AMH) is a hormone produced by small
follicles in the ovary which contain eggs. The amount of AMH
gives an indication of the number of eggs being produced, or
ovarian reserve, and can be tested at any point in a woman’s cycle
 It does NOT test whether you are ovulating or not; rather it is
designed to see if your ovaries are in good shape or not.
 AMH is measurable from birth to near the menopause, with a peak
in the mid-20s, and from the age of 25 levels begin to decline.
From the age of 35 AMH declines steadily until it reaches zero at
the menopause.
 AMH levels decline at predictable rates hence the AMH test is
a good snapshot of current fertility.
• One recent article described continuous use of combined
contraception (i.e. without monthly breaks) was associated with a
reduction of AMH levels.
• Women under the age of 35 may be tested to determine ovarian
reserve which may assist to determine optimal timing to start a
family. The test can also be helpful in determining the fertility
status of patients at risk of diminished ovarian reserve e.g.
women with a history of ovarian failure, family history of early
onset menopause, auto immune disease, women who have
undergone chemotherapy or had ovarian surgery. It is also
helpful for Polycystic Ovary Syndrome patients.
It is a single blood test that can be done at any time during the
menstrual cycle, used to:
 Determine fertility status
 Determine a patient’s response to fertility medication
 It can also help to predict how many eggs you are likely to obtain
in an IVF cycle.
 It may also identify women who may undergo early menopause,
and therefore who may lose their fertility earlier than average.
Although an AMH test can help pick up those who might lose their
fertility more quickly, it cannot show who is more fertile than average
, nor does it predict ovarian reserve in women with polycystic Ovaries
(PCO)
Each month at ovulation, chance of conception is based upon both
the health of the egg and the ovarian environment in which the egg
developed.
Ovarian reserve is another fundamental factor linked to fertility.
Ovarian reserve refers to a woman’s current supply of eggs within
her ovaries and is closely associated with reproductive potential.
In general, the greater the number of eggs remaining, the better the
chance for conception.
As a woman ages, her supply diminishes over time, reducing her
fertility, until all of the eggs are depleted at menopause.
Determining Ovarian Reserve Through FSH and AMH
Clinical discordance in serum AMH and FSH values thus was frequent
and was age dependent.
FSH mostly reflects the last two weeks of follicular maturation
when follicles become gonadotropin sensitive, while AMH is
mostly representative of the young, post-primordial to preantral
follicle pool going through earlier stages of folliculogenesis.
Menstruation (From day 1 to 5)
Follicular phase (From day 1 to 13)
Ovulation phase (Day 14)
Luteal phase (From day 15 to 28)
Follicular Phase. The follicular phase begins with the first day of
menstrual bleeding:
At the start of the follicular phase, estrogen and progesterone
levels are at their lowest point. This causes the uterine lining to
break down and shed.
At the same time, the hypothalamus produces GnRH, which
stimulates the production of follicle-stimulating hormone (FSH)
and luteinizing hormone (LH).
FSH and LH trigger the production of estrogen.
As FSH levels increase, it stimulate the growth and maturation
of eggs in the follicles. About 15 - 20 follicles are stimulated, but
only one follicle continues to mature.
The dominant follicle produces estrogen. The other follicles stop
growing and disintegrate.
Ovulation is when a mature egg is released from the ovary, pushed
down the fallopian tube, and is available to be fertilized.
Approximately every month an egg will mature within one of your
ovaries. As it reaches maturity, the egg is released by the ovary where
it enters the fallopian tube to make its way towards the uterus.
As soon as the fertilized egg has implanted, your body starts
producing the pregnancy hormone, human Chorionic Gonadotrophin
(hCG), which will keep the empty follicle active.
It continues to produce the hormones estrogen and progesterone to
prevent the lining of the womb from being shed, until the placenta
(which contains all the nutrients the embryo needs) is mature enough
to maintain the pregnancy.
Ovulatory Phase. The ovulatory phase occurs halfway through the
menstrual cycle (about 14 days after the start of the follicular phase.)
Ovulation, the critical process for conception, occurs during the
ovulatory phase.
A woman’s fertile period starts about 3 - 5 days before ovulation and
ends 24 - 48 hours after it.
During the ovulatory phase:
The increase in estrogen from the dominant follicle triggers a surge
in LH. As estrogen levels rise, they also prompt the cervix to secrete
more mucus to help nourish and propel sperm to the egg.
The LH surge signals the dominant follicle to burst and release the
developed egg into the fallopian tube. The release of the egg is
called ovulation. Once in the fallopian tube, the egg is in place for
fertilization.
The egg can live for 24 - 48 hours after being released.(Sperm can
live for 3 - 5 days.)
A woman is most likely to get pregnant if sex occurs in the 3 - 5 day
s before ovulation or on the day of ovulation.
Luteal Phase. The luteal phase begins immediately after ovulation
and ends when the next menstrual period starts.
The luteal phase lasts about 12 - 16 days.
During the luteal phase:
After releasing the egg, the ruptured follicle closes and forms corpus
luteum, a yellow mass of cells that provide a source of estrogen and
progesterone during pregnancy. These hormones help the uterine
lining to thicken and prepare for the egg’s implantation.
If the egg is fertilized by a sperm cell, it implants in the uterus and
pregnancy begins.
If fertilization does not occur, the egg breaks apart. The corpus
luteum degenerates, and estrogen and progesterone levels drop.
Finally, the thickened uterine lining sloughs off and is shed along
with the unfertilized egg during menstruation. The menstrual cycle
begins again.
Luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
are called gonadotropins because stimulate the gonads (in males,
the testes, and in females, the ovaries).
They are not necessary for life, but are essential for reproduction.
Measuring the gonadotropic hormones FSH & LH help determine
whether a gonadal deficiency is of primary origin or is due to
insufficient stimulation by the pituitary hormones.
Measuring the levels of FSH and LH is of value in studying
children with endocrine problems related to precocious puberty.
In the case of anovulatory fertility problems, the presence or
absence of the mid cycle peak can be established through a
series of daily blood specimens.
• The principle regulator of LH and FSH
secretion is gonadotropin-releasing hormone
• Gonadotropin-releasing hormone secretion
is stimulated by a decrease in estrogen and
testosterone levels.
• GnRH stimulates secretion of LH & FSH
which in turn stimulates gonadal secretion
of the sex steroids testosterone, estrogen
and progesterone.
• In a classical negative feedback loop, sex
steroids inhibit secretion of GnRH and also
appear to have direct negative effects on
gonadotrophs.
FSH is a glycoprotein hormone, produced in the anterior
pituitary and released into the blood in response to GnRH
(GnRH is released from the hypothalamus).
FSH regulates the development, growth, pubertal maturation,
and reproductive processes of the human body.
In both males and females, FSH stimulates the maturation
of germ cells.
In males, FSH controls spermatogenesis
In females, FSH stimulate the growth and maturation of eggs
in the follicles
In female, the FSH is transported to the ovary, enters the developing
follicle, and stimulates the granulosa cells to produce estrogen.
Granulosa cells are a type of cells lining the follicle FSH is also
responsible for growth of the follicle, involving both an increase in the
number of granulosa cells and secretion of follicular fluid.
As the follicle grows, the granulosa cells secrete a hormone called
inhibin into the follicular fluid.
This hormone is carried, through the vascular system, back to the
anterior pituitary where it suppresses the secretion of FSH.
•In men, FSH partially controls spermatogenesis, but the presence of t
estosterone is also necessary.
• The test is usually performed on cycle day 3 but it can also be
performed on day 2, 3, or 4 of a woman's menstrual cycle.
• FSH test is usually carried out on the 3rd day of your menstrual
cycle as this gives the most accurate reading of your ovarian
reserve (number of eggs within your ovaries).
• FSH levels fluctuate throughout your cycle and peak at ovulation
• Your FSH level is measured along with your LH and estradiol.
• Day 3 estradiol test is exactly the same as the Day 3 FSH test.
• High levels of FSH/estradiol ratio mean poor quality ovarian
reserve. Low levels are better, say 3 mIU/ml to 10 mUI/ml. Mo
re than 12 mUI/ml indicates a problem and 25 mUI/ml means
ovarian failure.
• You may be asked to stop taking medicines (including birth cont
rol pills) that contain estrogen or progesterone or both for up to
4 weeks before having a follicle-stimulating hormone (FSH) test.
Because your FSH levels rise when your ovaries stop producing
enough estrogen, high FSH levels can signal that your body is
entering menopause.
As women approach menopause, their baseline FSH level will
gradually increase. When a woman goes into menopause she is
essentially running out of eggs and estrogen production in her
ovaries. Sensing a low estrogen environment, the brain releases
more FSH from the pituitary gland in an attempt to stimulate the
ovaries to produce a mature follicle and more estrogen.
Gonadal failure
Anterior pituitary hypofunction
Gonadotropin-secreting pituitary
tumors
Hyperprolactinemia
primary ovarian failure or testicular
failure
Hypothalamic disorders
Menopause!
Polycystic ovary disease
Precocious puberty in children
Pregnancy
Primary hypogonadism
• Similar to FSH, LH is produced in the anterior pituitary and is
glycoprotein hormone.
• LH is released due to the influence of GnRH from the hypothalam
us.
• The LH is transported to the ovary and stimulates the cells
surrounding the follicle to produce testosterone.
• Circulating concentrations of LH are low in the late luteal phase.
• Initial rise occurs in early estrus and reaches peak values after
ovulation.
• In the female, this hormone stimulates major follicular growth,
maturation and ovulation.
• It also responsible for initial formation of corpus luteum and stim
ulation of estrogen & progesterone secretion
• Values decrease as progesterone concentrations rise.
This hormone goes up fast just before ovulation occurs, about
midway through the cycle (day 14 of a 28-day cycle). This is called
an LH surge.
LH and FSH levels rise and fall together during the monthly cycle.
In men, LH stimulates the production of testosterone. which plays a
role in sperm production.
For women, more than one blood sample may be needed to get a true
reading of the luteinizing hormone (LH) levels.
If the test is being performed to detect ovulation, inform the patient t
hat it may be necessary to obtain a series of samples over a period of
several days to detect peak LH levels.
1. Help find the cause of infertility. FSH testing is commonly used
to help evaluate a:
•
•
Woman's egg supply (ovarian reserve).
Man's low sperm count.
2. Help evaluate menstrual problems, such as irregular or absent
menstrual periods (amenorrhea). This can help determine
whether the woman has gone through menopause.
3. Determine if a child is going through early puberty (also called
precocious puberty). Puberty is early when it starts in girls
younger than age 9 and in boys younger than age 10.
4. Determine why sexual features or organs are not developing
when they should (delayed puberty).
5. Help diagnose certain pituitary gland disorders, such as
a tumor.
Gonadal failure
Pituitary or hypothalamic dysfunction
Menopause
Severe stress
Drugs and hormones : clomiphene,
gonadotropin-releasing hormone
Drugs and hormones:
anabolic steroids, anticonvulsants, conjugated
estrogens,, estrogen/progestin therapy, oral
contraceptives, progesterone
Primary gonadal dysfunction
Leutinizing Hormone (LH): normal day 3 LH levels are 5-20 mlU/ml.
day 3 LH and FSH analysis, In PCOS testing, the LH:FSH ratio may
be used in the diagnosis. The ratio is usually close to 1:1, but if the LH
is higher, it is one possible indication of PCOS
Hormones time of collection
FSH,
At 5,6,7 days of cycle
LH
At 13,14 days of cycle
Estradiol
At 9,10,11 days of cycle
progesterone
21 of cycle
Estrogen is produced mostly by the ovaries and during pregnancy by p
lacenta.
Estradiol is also secreted in minute amounts by the a drenal cortex and
the testes.
Only three types of estrogen are present in the blood in measurable a
mounts: estrone, estradiol, and estriol.
Estradiol is the most active of the estrogens. Estrone (E1) is the imme
diate precursor of estradiol (E2). Estriol (E3) is secreted in large amou
nts from the placenta during pregnancy from precursors produced by
the fetal liver.
Estradiol is secreted in a biphasic pattern during normal menstruation.
Knowledge of the phase of the menstrual cycle may assist interpretati
on of estradiol levels.
Female sex organs development: at puberty, increase in size of fallopian tub
es, uterus and vagina, external genitalia deposition of fat.
endometrium: proliferation of cells and endometrial glands (important in n
utrition of fertilized ovum)
Breasts: fat deposition, development of stromal cells growth of an extensiv
e ductile system, promotes growth and further maturity of the breasts in p
reparation for milk production.
One of the main roles of estrogen is to regulate progesterone. Progesteron
e in synchrony with estrogen is necessary to initiate fetal maturation. With
out them, a fetus’s lungs, liver and other organs and tissues cannot mature.
Bone: Estrogens inhibit osteoclastic activity in the bones and therefore sti
mulate bone growth
After menopause, almost no estrogens are secreted by the ovaries.
This estrogen deficiency leads to increased osteoclastic activity in the bone
s and decreased deposition of bone calcium and phosphate. Could results o
steoporosis.
• Progesterone is a female sex hormone, is primarily involved in the
preparation of the uterus for pregnancy and its maintenance during
pregnancy.
• The placenta begins producing progesterone at 12 weeks of gestation.
• Levels of progesterone in twin pregnancy are higher than in a single
pregnancy.
• Progesterone level peaks in the midluteal phase of the menstrual cycle
produced by the corpus luteum and levels are low during the follicular
(first) phase of the menstrual cycle “corpus luteum regresses,
progesterone levels fall.
• After ovulation, progesterone levels rise for 4 to 5 days, the lining of
the uterus has thickened to prepare for the fertilized egg. If no
conception occurs, the uterine lining, as well as blood, will be shed,
the shedding of an unfertilized egg and the uterine wall “Menstruation
 Progesterone function is to:
• Prepare the uterus for pregnancy and the breasts for lactation.
• Stimulate uterine glands secretion
• Growth of the breast alveoli
• Inhibition of uterine muscles contractions during pregnancy to
prevent expulsion of the fetus
 Uses:
• To confirm that ovulation has occurred and to assess the functioning
of the corpus luteum.
• Serial measurements can be performed to help determine the day of
ovulation.
• Monitor patients receiving progesterone-replacement therapy
• Assist the diagnosis of luteal phase defects (performed in conjunction
with endometrial biopsy)
• Evaluate patients at risk for early or spontaneous abortion
• Identify patients at risk for ectopic pregnancy “along with hCG” and
assessment of corpus luteum function