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Reproduction > Sex Hormones and Disease > Flashcards

Sex Hormones and Disease Flashcards

1
Q

What are the benefits of postmenopausal HRT?

A

Improved bone density (decreased resorption); relief from flushes, fatigue, vaginal dryness by re-estb feedback control; reversal of atrophy of vulva, vagina, and urethra; improved sleep and pattern; reduced incidence of colorectal cancers; +/-reduced incidence of CHD and Alzheimer’s

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2
Q

What are the risks of postmenopausal HRT?

A

breast tenderness, nausea, fluid retention; increased risk of breast or uterine cancer; increased risk of thromboembolism and stroke

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3
Q

What is the mechanism of action of estrogen?

A

oestrogen crosses the plasma membrane; binds estrogen receptor (ER) in cytoplasm; receptors form homodimers which bind to specific oestrogen response elements (ERE) to activate gene transcription to mRNA

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4
Q

T/F oestrogen bound to its ER can form heterodimers

A

True, with different transcription factors to up or downregulate gene transcription - may be related to different types of oestrogen (less abundant forms)

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5
Q

Tissue specific effects of oestrogen arise due to

A

receptor subtypes - ER alpha and ER beta with differential affinities; multiple co-factors; can cause gene activation or repression

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6
Q

Rapid effects of oestrogen eg neuronal actions where oestrogens cause rapid Ca2+ influx causing rapid dilation are attributed to

A

in certain tissues, there are ER on the cell membrane; oestrogen may also be able to act via GPR30, a GPCR

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7
Q

Oestrogen binding ER generally promotes

A

growth and expression of the progesterone receptor PR

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8
Q

Progesterone receptors are upregulated by

A

oestrogen binding ER

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9
Q

Progesterone binding PR stimualtes

A

growth and differentiation

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10
Q

What is significant about ER and PR expression post menopausal?

A

Expression of both receptors goes up post-menopause in patients with breast cancer

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11
Q

Tamoxifen, Raloxifene

A

ER partial agonists used in tx of breast cancer; both have antagonistic effects on ER receptors in breast tissue

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12
Q

Fulvestrant

A

ER antagonist in trials for tx of breast cancer; antagonistic effects in breast, uterus, bone, CV, and CNS tissue

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13
Q

Tamoxifen is used as

A

palliative tx of metastatic breast cancer and adjuvant following lumpectomy

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14
Q

Tamoxifen acts as

A

an antagonist in breast but partial agonist in bone and endometrium

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15
Q

What are the adverse effects of tamoxifen?

A

Endometrial hyperplasia, polyps, and cancer; thromboembolic events; thrombocytopaenia; ocular toxicity; menopausal symptoms (hot flushes, atrophic vaginitis)

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16
Q

T/F resistance can develop to tamoxifen

A

True; tumours can recur because there are multiple receptors and transcription factors in the mechanism of action

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17
Q

Aromatase is active in

A

breast adipose mesenchymal cells

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18
Q

Why are blood oestrogen levels in post-menopausal women inaccurate?

A

Oestradiol may act as a paracrine hormone therefore while plasma oestrogen may be low, cellular levels will be high due to aromatase activity

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19
Q

Exmenostane is

A

an aromatase inhibitor

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20
Q

Exmenostane is used in

A

tx of breast cancer because it reduces levels of all oestrogens by reducing their synthesis thus decreasing the potential of ER stimulation in breast tissue

21
Q

What are the benefits of exemestane in tx of breast cancer?

A

improvement in disease-free survival after tamoxifen tx; reduced incidence of contralateral breast cancer, number of thromboembolic events, and incidence of endometrial cancer

22
Q

What are the risks of using exemestane tx in breast cancer?

A

Increased bone loss & fracture risk; increased arthralgia and joint damage; potentially poorer lipid profile, hepatic steatosis, and metabolic syndrome with long term use; menopausal signs

23
Q

Dihydrotestosterone is active in

A

prostate, seminal vesicles, epididymis and skin

24
Q

Testosterone circulates in blood on

A

steroid hormone binding globulin

25
Q

What is the mechanism of action of testosterone?

A

dissociates from SHBG in blood to cross the membrane; in some tissues 5a reductase converts it to dihydrotestosterone; DHT binds the androgen receptor; the receptor dimerizes and the complex translocates to the nucleus to alter gene transcription

26
Q

What actions of testosterone are specific to the testosterone form?

A

Gonadotrophin release (-ve fbk)
Spermatogenesis
Sexual differentiation
Anabolic effects

27
Q

What actions of testosterone are specific to the DHT form?

A

Prostate development
External virilisation
Sexual maturation

28
Q

T/F testosterone can directly activate androgen receptors in the nucleus

A

True; there is an equilibrium between receptors in the cytoplasm and the nucleus - testosterone can bind both of these receptors

29
Q

Therapeutic uses of androgens for androgenic effects include

A

hypogonadism

30
Q

Therapeutic uses of androgens for anabolic effects include

A

senile osteoporosis to promote bone growth; speeding recovery from surgery and chronic debilitating diseases

31
Q

Therapeutic uses of androgens for growth effects include

A

promoting skeletal growth in pituitary dwarfism

32
Q

Androgen use in endometriosis aids

A

reduce pain and inflammation; may increase local oestrogen production to restore balance

33
Q

What are the therapeutic uses of oestrogens?

A

Hypogonadism in children for development of sex characteristics and accelerating growth; primary amenorrhoea, contraception, and menopause in adults

34
Q

Adverse coronary effects of androgens include

A

increased LDL and decreased HDL tf increasing risk of CHD

35
Q

Adverse effects of androgens in females include

A

acne, facial hair, deepening of voice, male pattern baldness, excessive muscle development, menstrual irregularities

36
Q

Adverse effects of androgens in males include

A

priapasm, impotence, decreased spermatogenesis, gynaecomastia

37
Q

Adverse effects of androgens on children include

A

premature closure of epiphyses, abnormal sexual maturation

38
Q

Adverse effects of androgens on athletes include

A

liver damage, increased aggression, psychotic episodes

39
Q

Anti-androgen receptor antagonists include

A

cyproterone and flutamide

40
Q

Cyproterone is a

A

steroidal antagonist with relative selectivity for androgen receptors

41
Q

Cyproterone is used for

A

prostate cancer and androgenisation in females (PCOS)

42
Q

What are the adverse effects of cyproterone?

A

cognitive changes, fatigue, oedema, reduced spermatogenesis

43
Q

Flutamide is a

A

non-steroidal antagonist thought to selectively block androgen receptors in prostate rather than throughout the body

44
Q

Flutamide is used in

A

metastatic prostate cancer

45
Q

What are the adverse effects of flutamide?

A

Diarrhoea, anaemia, hepatic injury, odema, dizziness, blurred vision

46
Q

5alpha reductase inhibitors

A

anti-androgen; blocks conversion of testosterone to dihydrotestosterone

47
Q

Finasteride is a

A

5alpha reductase inhibitor that blocks conversion of testosterone to DHT

48
Q

Finasteride is used in

A

benign prostatic hypertrophy (remember that DHT is abundant in prostate, SV, and epididymis); hair loss (assoc with high DHT) treatment

49
Q

What are the adverse effects of 5alpha reductase inhibitor finasteride?

A

impotence, decreased libido, ejaculation disorder; breast enlargement and tenderness; breast cancer because testosterone is now converted to oestrogen in breast tissue instead of DHT

Reproduction (11 decks)

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