Pharmacology of Sex Hormones (L2)

its recommended that _____________ be offered as first-line methods of contraception to all women, including adolescents

LARCs (IUDs and implant)

hormonal IUDs and subdermal implant prevents pregnancy by thickening ___________ and thinning _____________ and by partially stopping ovulation

cervical mucus, uterine lining

which LARC is ok to use in someone with breast cancer

copper IUD

perimenopause is the period preceding menopause

common symptoms include ________, irregular periods, mood swings, brain fog, and __________

hot flashes, osteoporosis

perimenopause is the period preceding menopause

there is a sharp decline in ovarian mass and fertility after age ______

35

HRT: meds containing female hormones to replace the ones the body no longer makes after menopause

estrogen-based HRT is primarily used for treatment of ___________ symptoms and for the prevention of ____________

vasomotor, urogenital, osteoporosis

HRT: meds containing female hormones to replace the ones the body no longer makes after menopause

__________-based HRT is primarily used for treatment of vasomotor and urogenital symptoms and for the prevention of osteoporosis

estrogen

HRT: meds containing female hormones to replace the ones the body no longer makes after menopause

estrogen-based HRT is primarily used for treatment of vasomotor and urogenital symptoms and for the prevention of osteoporosis

HRT doses have x2 _______ estrogen than OCPs do

less

HRT: meds containing female hormones to replace the ones the body no longer makes after menopause

progestin should be added for protection of the _____________ in order to reduce instances of hyperplasia and carcinoma

endometrium

HRT: meds containing female hormones to replace the ones the body no longer makes after menopause

__________ should be added for protection of the endometrium in order to reduce instances of hyperplasia and carcinoma

progestin

one risk associated with using HRT in menopausal women is endometrium cancer, which is why we should add ___________

progestin

_____________ is the gradual decrease of free testosterone with age (results in sexual dysfunction, obesity, loss of muscle mass, loss of body hair, depression)

hypogonadism

hypogonadism is the gradual decrease of free ___________ with age (results in sexual dysfunction, obesity, loss of muscle mass, loss of body hair, depression)

testosterone

______________ can be used to treat hypogonadism in men

TRT (Testosterone Replacement Therapy)

TRT can be used to treat ___________ in men

hypogonadism

breast cancer, prostate cancer, uncontrolled HF, untreated OSA, and/or elevated prostate specific antigen are all contraindications to which therapy

TRT

Oral Contraceptives have a tri-pronged MOA

1. suppression of _________

2. changed turbidity of____________

3. alteration of the ____________

ovulation, cervical mucus, endometrium

the estrogen and progestin component of OCs are ________

synthetic

combination OCs suppress _________ and _________

LH and FSH (absence of mid-cycle LH surge)

combination OCs suppress LH and FSH; there is an absence of the mid-cycle ________________ required for ovulation

LH surge

MOA of estrogens in combination OCs

primary function is to stabilize _______________ and provide cycle control

is also suppresses ________ release from the pituitary, which may contribute to the blocking of the LH surge which prevents ovulation

endometrium lining, FSH

MOA of ___________ component in combination OCs

primary function is to stabilize endometrium lining and provide cycle control

is also suppresses FSH release from the pituitary, which may contribute to the blocking of the LH surge which prevents ovulation

estrogen

MOA of progestin component in combination OCs

primary function is to provide the ___________ effect

contraceptive

MOA of ___________ component in combination OCs

primary function is to provide the contraceptive effect

progestin

MOA of progestin component in combination OCs

primary function is to provide the contraceptive effect

1. progestins bind to PR in the cells of the cervix and lead to production of thick ________, which prevents sperm penetration and slows transport though the ___________

mucus, fallopian tubes

MOA of progestin component in combination OCs

primary function is to provide the contraceptive effect

1. progestins bind to PR in the cells of the cervix and lead to production of thick mucus, which prevents _______________ and slows transport though the ___________

sperm penetration, fallopian tubes

MOA of progestin component in combination OCs

primary function is to provide the contraceptive effect

2. progestins bind PR receptors in the uterine lining and counteract proliferative signals of E2, leading to __________ and _________ of the endometrium

thinning, atrophy

MOA of progestin component in combination OCs

primary function is to provide the contraceptive effect

2. progestins bind PR receptors in the uterine lining and counteract proliferative signals of E2, leading to thinning and atrophy of the ________________

endometrium

MOA of progestin component in combination OCs

primary function is to provide the contraceptive effect

3. progestins diminish the frequency of ________ pulses in the HPGA in the brain using the negative feedback loop

GnRH (thus blocking LH surge)

some absolute contraindications to OCs

- MI, _________, history of CAD, or history of ____________ (basically any CV stuff)

- tumors of the liver or impaired liver function

- known or suspected cancers or pregnancy

- migraines

- smoking

- unmanaged ________

stroke, blood clots, HTN

some absolute contraindications to OCs

- MI, stroke, history of CAD, or history of blood clots (basically any CV stuff)

- tumors of the _______ or impaired _______ function

- known or suspected cancers or pregnancy

- migraines

- smoking

- unmanaged HTN

liver

some absolute contraindications to OCs

- MI, stroke, history of CAD, or history of blood clots (basically any CV stuff)

- tumors of the liver or impaired liver function

- known or suspected _______ or __________

- migraines

- smoking

- unmanaged HTN

cancer, pregnancy

___________ are used in the treatment of infertility, ovulation induction in IVF, or testosterone production and sperm development

gonadotropins

____________ can be used to stimulate testosterone production and sperm development (upstream regulatory agent)

gonadotropin

why do ovaries in menopause not respond to LH and FSH

ovaries run out of functioning follicles, so the target of LH and FSH are gone

ovaries in menopause do not respond to LH and FSH since the ovaries have run out of functioning follicles, so the target of LH and FSH are gone

at ____________ age: estrogen and progestin in the negative feedback loop shut off LH and FSH production

at ____________ age: estrogen and progestin are not being produced and therefore are unable to activate the negative feedback loop (andddd LH and FSH just keep getting produced with no where to go)

reproductive, menopause

GnRH agonists (2-phases) are mainly used for metastatic _____________ cancer

prostate

GnRH-___________ are mainly used for metastatic prostate cancer

agonists (2-phases)

GnRH agonists are mainly used for metastatic prostate cancer

are these direct or do they have 2 phases

2 phases (initially promotes LH/FSH, later decreases LH/FSH)

GnRH antagonists are mainly used in IVF procedures, to treat fibroids, endometriosis, and against active prostate cancer

MOA: are these direct or do they have 2 phases

direct

GnRH agonists (2 phases) are mainly used for metastatic prostate cancer

initially they _________ LH and FSH

later (after ~10 days) they __________ LH and FSH (therapeutic goal)

increase, decrease

GnRH-___________

initially they increase LH and FSH, which can cause tumor flare effect

later (after ~10 days) they decrease LH and FSH d/t desensitization and internalization (therapeutic goal)

agonists (they are technically functionally like GnRH-antagonists if you think about it lol)

GnRH-______________ are mainly used in IVF procedures, to treat fibroids, endometriosis, and against active prostate cancer

antagonists (direct)

GnRH antagonists (direct) are mainly used in IVF procedures, to treat fibroids, endometriosis, and against active prostate cancer

they competitively and reversibly bind to GnRH receptor to block release of _____________ from the ___________

LH and FSH, pituitary

SERMs differ from estrogens in their MOA since they act as __________

modulators (they can act as estrogen stimulators in some tissues or inhibitors in others)

_____________ differ from estrogens in their MOA since they act as modulators

SERMs

_____________ act as modulators and can act as estrogen stimulators in some tissues or inhibitors in others

SERMs

SERMs are modulators that can act as estrogen stimulators in some tissues or inhibitors in others

they are used to prevent and/or treat __________-related disorders like breast cancer, gynecomastia, or postmenopausal osteoporosis

estrogen

Tamoxifen (used to treat breast cancer) is a ________________, which can also lead to the development of uterine cancer

SERM (Selective Estrogen Receptor Modulator)

aromatase inhibitors act ____stream by either inhibiting (reversible) or forming a permanent bond (irreversible) with the enzyme aromatase

down (they work after testosterone/androstenedione has already been synthesized)

__________________ act downstream by either inhibiting (reversible) or forming a permanent bond (irreversible) with the enzyme ________

aromatase inhibitors, aromatase

aromatase inhibitors act downstream by either inhibiting (reversible) or forming a permanent bond (irreversible) with the enzyme aromatase

that enzyme is responsible for the conversion of ___________ into _______________ in breast/peripheral tissues in menopausal women

testosterone (&androstenedione), estradiol

aromatase inhibitors act downstream by either inhibiting (reversible) or forming a permanent bond (irreversible) with the enzyme aromatase

that enzyme is responsible for the conversion of testosterone (&androstenedione) —> estradiol in _________ and __________ tissues in menopausal women

breast, peripheral (does NOT turn off aromatase in the ovaries or in pre-menopausal women)

can aromatase inhibitors be used in pre-menopausal women (reproductive age), post-menopausal women, or either

post-menopausal

_________________ inhibit circulating androgens by blocking androgen receptors, suppressing androgen synthesis, or acting in both of these ways

antiandrogens

antiandrogens inhibit circulating androgens by blocking androgen ___________, suppressing androgen ___________, or acting in both of these ways

receptors, synthesis

T or F: the first part of GnRH agonists MOA is an upregulation of LH and FSH

T

T or F: the first part of GnRH agonists MOA is a downregulation of LH and FSH

F

T or F: the second part of GnRH agonists MOA is an upregulation of LH and FSH

F

T or F: the second part of GnRH agonists MOA is a downregulation of LH and FSH

T

you want to effectively block LH and FSH production in a patient, what is the best option?

a. GnRH agonists

b. GnRH antagonists

c. Aromatase inhibitors

d. SERMs

B (GnRH agonists would initially spike the LH/FSH for 10 days) (aromatase inhibitors and SERMs work after LH and FSH have already been synthesized)