Part 17: Gonadal Hormones Flashcards
the gonadal hormones are also known as ____
sex hormones
t/f sex hormones are involved in more than just reproduction
t
LH and FSH are secreted by the ____ gland to act on the ___ and ___
pituitary; testes & ovaries
stimulation of ovaries & testes by LH and FSH causes them to release ___
estrogens and androgens
sex hormones exist in a ___ feedback system
negative
androgens and estrogens cause negative feedback by looping back to the ___ and ___ glands
pituitary and hypothalamus
the frequency of ____ from the hypothalamus detrmines which pituitray hormone is released
pulsatile release of gonadotropin releasing hormone
what releases GnRH?
hypothalamus
what releases LH and FSH?
pituitary gland
what is the role of LH?
androgen release, ovulation
what is the role of FSH?
follicle development & spermatogenesis
which hormone will be released by pituitary if there is a high frequency of GnRH release from the hypothalamus?
LH
which hormone will be released by pituitary if there is a low frequency of GnRH release from the hypothalamus?
FSH
which hormones are released from the pituitary if there is constant release of GnRH from the hypothalamus?
neither FSH or LH
give 2 examples of what synthetic GnRH can be used to treat
infertility; some types of hormone sensitive cancer
what is the main role of FSH in males?
starting puberty and sperm maturation
____ is the primary hormone that stimulate the making of testosterone
LH
where is testosterone made?
Leydig cells of the testes
testosterone is made from ___
cholesterol
testosterone circulates in the blood by being bound to ___ protein
sex hormone binding globulin (SHBG)
testosterone binds to ___ receptors
intracellular androgen receptors
once inside target cells, testosterone is converted to ___ by ___ enzymes
dihydrotesterone (DHT); 5-alpha reductases
which is a higher potency agonist at androgen receptors, testosterone, or DHT?
DHT
the activated androgen-receptor complex is translocated to the ____ where it modifies gene ___ and ___ synthesis
nucleus, transcription; protein synthesis
t/f many of the androgenic effects we often associate with testosterone are actually caused by DHT
t
which androgen is responsible for the development of male secondary sex characteristics?
DHT
testosterone is important in early development and throughout life it is involved in the production and maintenance of ___, ___ , __and ___
muscle mass; red blood cells; bones; hair growth
testosterone can also be metabolized by CYP19 (aromatase) into ___
estradiol
the estrogens made from testosterone is important for ___ in males
bond density
the levels of estrogen in males is typically ____ (high or low)
low
t/f aromatase enzymes are expressed in fat cells, so obese men can express more estrogen and a decrease in testosterone
t
what are the 2 categories testosterone modulation falls into?
replacement or suppression therapy
androgen ____ therapy is used for low T syndrome
replacement
androgen ____ therapy is used for performance enhancement
replacement
androgen ____ therapy is used for treatment of prostate enlargement
suppression
androgen ____ therapy is used for treatment of hormone sensitive prostate cancer
suppression
what is low T syndrome?
circulating levels of testosterone are insufficient to maintain normal physiologic roles of androgens
t/f testosterone levels dcline with age
t
what are some of the symptoms of low T?
low sex drive, fatigue, hair loss, reduced muscle mass
t/f replacing testosterone can effectively manage low T symptoms
t
t/f the lipophilicity of steroid hormones make it possible to administer them transdermally
t
what are the benefits of transdermal testosterone?
slow release, easy, avoids 1st pass metabolism
what is a major downfall of oral testosterone treatment?
most will be metabolized before reaching systemic circulation
how is testosterone for performance typically administered?
high dose my IM injection
why is testosterone for performance typically given IM?
to target the muscle they want to grow and avoids 1st pass metabolism
what is Androderm?
testosterone transdermal patch
t/f androgens are involved in prostate enlargement
t
what is benign prostatic hyperplasia (BPH)?
a benign prostate enlargement
what is a common symptoms of enlarged prostate?
urinary retention
why does enlarged prostate cause urinary retention?
obstruction of the urethra
does prostate cancer have a high level of metastasis?
yes
ketoconazole and spironolactone are anti-androgens that work by what way?
inhibit testosterone biosynthesis
what is a concern when usifg ketoconazole to inhibit testosterone synthesis?
a CYP3A4 inhibitor which can lead to a lot of interactions
why are ketoconazole and spironolactone not commonly used as androgen suppressors?
they both have other systemic effects and there are drugs that are more specific to target androgen production
how is finasteride used as an anti-androgen?
inhibits the conversion of testosterone to DHT by inhibiting the 5-alpha reductase enzymes
how does flutamide work as an anti-androgen
androgen receptor antagonist
an important consideration when using finasteride or flutamide as anti-androgens is that blocking these pathways allows for more ____
free testosterone that can be converted into estradiol
what is a side-effect of finasteride and flutamide as a result of increased estradiol?
increased breast tissue
what are the 5 hormones involved in female reproduction?
progestins, estrogens, human chorionic gonadotropin (hCG), oxytocin, prolactin
which female hormones are directly involved in the menstrual cycle and female reproductive development?
progestins and estrogens
____ is a hormone produced during early embryo development, is excreted in urine and is used in at-home pregnancy tests
human chorionic gonadotropin (hCG)
what hormone is involved in uterine contractions during birth?
oxytocin
what hormone is involved in milk production and lactation?
prolactin
what are the 4 stages of the menstrual cycle in order?
follicle development, ovulation, endometrium proliferation, and menstruation
what is the important hormone during the follicular phase?
FSH
follicle secrete what hormone as they develop?
estrogen
increased estrogen levels results in a ____ feedback on FSH levels and ____ feedback of LH levels
negative; positiev
LH spike triggers ____
ovulation
after ovulation, ___ and ____ levels rise
progesterone and estrogen
estrogen and progesterone is secreted by the ____
corpus luteum
what is the effect of estrogen and progesterone release after ovulation?
endometrial changes that favour implantation of a fertilized egg
a drop in ___ and ___ hormones initiates menstruation
estrogen and progesterone
t/f estrogen and progesterone have negative feedback effects throughout most of the menstrual cycle
t
during follicle development, there is a ___ feedback loop between estradiol and LH, resulting in the LH surge needed for ovulation
positive
estrogen and progesterone have nagative feedback loops on ___ and ___
FSH and GnRH
estrogens and progesterone are produced mainly in the ____
ovaries
is testosterone produced in the ovaries?
yes actually
___ is the starting material for estrogen, testosterone, and progesterone
cholesterol
____ enzymes are used in the process of making estrogen
aromatases
t/f there are many similarities between the male and female hormone systems, but it is teh balance of the hormones made that makes the difference
t
bc androgens and estrogens are made by the same pathway, altering production of one will have an impact om the other
t
what is the most common pharm modulation of estrogens and progestins?
hormonal contraceptives to prevent pregnancy
estrogens and progesterones used as hormone replacement are typically dosed ___ (higher or lower) than contraceptives
lower
give 2 examples of local progestin administration for birth control
IUD and nuva ring
how does hormonal contraception work?
reinforces the negative feedback loop to prevent LH surge, which inhibits ovulation, no egg, no pregnancy
progestin-containing contraceptives have negative feedback on ___ and ___ hormones
LH and FSH
what is the main goal of hormonal contraception?
increase the negative feedback loop so the positive feedback loop does not occur and ovulation is prevented
estrogen ___ the endometrium
increses
progesterone ___ the endometrium
decreases (lighter periods)
if estrogen was given alone, it could cause ___
endometrial cancer
t/f estrogen is always given at the lowest effective dose and always with progesterone
t
the continual presence of progesterone makes the uterus unfavourable for _____
implantation of a fertilized egg
progesterone ____ the movement of sperm
slows
progesterone ____ cervical mucus production
increases
what is ethinyl estradiol?
an estrogen used for contraception
t/f progestin only products need to be taken at the same time every day to maintain adequate hormone levels
t
depot injections typically last ___ weeks
12
IUDs like mirena last up to ___ years
5
what is the most common side effect with prolonged progestins?
breakthrough bleeding or spotting related to the shedding of the endometrial lining
t/f the breakthrough bleeding of progestins typically resolves over time
t
t/f many patients using IUD or depot tend to cease menstruation all together
t
give an example of a progestin only contraceptive
micronor: norethindrone
androgenic progestins may increase ___ and ___ as side effects and non-androgenic progestins have the oppposite effects
weight gain & acne
what is the active ingredient in the depo-provera shot?
medroxyprogesterone acetate
what is the active ingredient is the Mirena IUD?
levonorgestrel
when a contraceptive with a progestin that is highly structurally similar to progesterone, it can be metabolized into _____ in the body
testosterone
when the progestin in BC is converted into testosterone, it can cause what side effects?
weight gain, acne, hair growth
are non-androgenic progestins structuarlly related to progesterone? Can they be converted into testosterone?
no ; no
give an example of an androgenic progestin?
norethindrone
give an example of a non-androgenic progestins
dropirenone
t/f the combination estrogen and progestin hormonal contraceptives are the most common birth control pills
t
t/f ethinyl estradiol is commonly used, but many different progestins are used
t
t/f there are many different varieties of dosing regimens
t
t/f combination birth controls cause an “artificial menstrual cycle”
t
what are the active ingredients in Yaz?
ethinyl estradiol & drospirenone
how does combination BC like Yaz work?
phasic cycles of hormone levels mimic physiologic levels to maintain the menstrual cycle but prevent the LH spike that would cause ovulation
what are some common side effects of elevated estrogen from BC? Are they reversible?
nausea, edema, migraines; usually resolve after prolonged use or when the dose is lowered
what are some of the serious side effects of estrogen in BC? What increases these risks?
CV (MI, blood clots, stroke); smoking and being older than 35 years
what can be done if a patient on a combo BC continues to have migraines and increased CV risk?
can be switched to progestin only pill
what is the failure rate of OCs?
7%
what is the failure rate of barrier methods like condoms?
13%
what can cause low hormone levels leading to contraceptive failures?
missing pills or improper administration, drug interactions, or other physiologic changes
t/f blood monitoring for hormone levels following BC use is possible, but not done unless there is a compelling reason
t
estrogens and progestin are metabolized by ____ enzymes, meaning many drug interactions are possible
CYP3A4
are CYP3A4 inducers or inhibitors more likely to decrease BC hormones?
CYP3A4 hormones
if using a combo BC rather than just progesterone, you are ___ (more or less ) likely to avoid failure due to drug interactions
less
the effect of enterohepatic circulation would be ____ (more or less) prominent when using an alternative dosage form like the IUD or depo shot
less
t/f the Mirena also prevents egg implantation by providing a physical barrier
t
the overall effectiveness of IUDs like Mirena is reported to be greater than ___
99%
is antibiotic use while on BC directly linked to failure leading to pregnancy?
no
what is the fail rate of depot progestin injections?
4%
what is the failure rate of surgical sterilization?
0.1-0.5%
what is the effect of phenytoin on BC?
CYP3A4 inducer (reduce circulating hormones)
what is the effect of antibiotics on BC?
reduce GI enterohepatic circulation hormones and increase CYP3A4
which antibiotic has been linked to possible contraceptive failure?
rifampin
