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CPT > L6 - Sex Steroids > Flashcards

L6 - Sex Steroids Flashcards

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1
Q

What are sex steroids derived from

A

Cholesterol

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2
Q

Sex steroids

A

Progesterone
Oestradiol
Testosterone

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3
Q

Oestrogen post menopause

A

Estrone - less potent

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4
Q

Sex steroid mechanism of action

A
  1. Hydrophobic therefore can pass through the cell membrane
  2. Bind to a nucleur receptor
  3. Activate gene transcription therefore gene expression
  • lag between exposure of the agonist and interactions downstream effect
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5
Q

Effects of oestradiol

A
  • endometrium proliferation
  • thin cervical mucus
  • proliferation of breast tissue
  • myometrium contractions
  • stimulates the expression of progesterone receptors
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6
Q

Effects of progesterone

A
  • inhibits myometrium contractions
  • production of thick acidic cervical mucus
  • stimulates growth of secretory glands in endometrium
  • maintains pregnancy
  • inhibits expression of oestrogen receptors
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7
Q

Testosterone

A

Stimulates male characteristics:

  • facial and body hair
  • deep voice
  • anabolism
  • aggression
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8
Q

Oestrogen secondary actions

A
  • mildly anabolic
  • sodium and water retention
  • raises HDL
  • lowers LDL
  • inhibits osteoclasts activity’s therefore maintains bone density
  • impairs glucose tolerance
  • increases blood glucose coagulability
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9
Q

Oestrogen side effects

A
  • tender breasts
  • nausea and vomiting
  • water and retention
  • increased risk of DVT and thromboembolism
  • impaired glucose tolerance - diabetes
  • endometrial hyperplasia - cancer
  • ovarian metaplasia - cancer
  • breast hyperplasia - cancer
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10
Q

Progesterone secondary actions

A
  • stimulates secretory gland formation in endometrium
  • anabolic
  • increases bone mineral density
  • fluid retention
  • mood changes
  • inhibits myometrium contractions to maintain pregnancy
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11
Q

Side effects of progesterone

A
  • weight gain - anabolic
  • fluid retention - oedema
  • acne
  • nausea and vomiting
  • irritability, depression and PMS
  • lack of concentration
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12
Q

Testosterone actions and side effects

A
  • male secondary sex characteristics
  • anabolic
  • acne
  • voice changes
  • increased aggression
  • lower HDL: LDL ratio - increased risk of atherosclerotic disease
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13
Q

Mechanisms of oestrogen entry

A
  • well absorbed in the GI tract - oral intake

- hydrophobic - readily absorbed from skin and mucous membranes - can be given in patches

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14
Q

Metabolism and excretion of oestrogen

A

Metabolism:
- occurs in the liver - drug is conjugated for excretion (phase 2 metabolism)

Excretion:
- in the urine via glucuronides and sulfates

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15
Q

Pharmacokinetics of progesterone

A

Injected progesterone is bound to albumin
Some stored in adipose tissue
Metabolised in liver
Excretes in the urine when conjugated to glucuronic acid

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16
Q

COCP side effects

A 
Small risk of thromboembolism 
Increased risk:
- smoking 
- prolonged use in over 35 year olds
- obese
- hypertension
17
Q

Metabolism of oestrogen and progesterone

A

CYP 450 enzymes in the liver

18
Q

Reduction in contraceptive efficacy

A

CYP 450 enzyme inducing drugs such as:

  • carbamazepine or phenytoin ( anti- epileptic)
  • rifampin and rifabutin
  • St John’s Wort (anti depressant)

More oestrogen and progesterone is metabolised as there is increased production in CYP 450

19
Q

Soya protein

A

Enhances oestrogen absorption
Reduces storage in adipose tissue and muscles - decreased Vd
Decreases half life from 15 to 7 hours

20
Q

Why is hormone replacement therapy given?

A

Unmanageable symptoms of:

  • hot flushes
  • sweats
  • dyspareunia
  • insomnia
  • protective against osteoporosis - oestrogen inhibits osteoclasts activity
  • not protective against heart disease
21
Q

Steroids used in hormone replacement therapy

A

Oestradiol:

  • valerate
  • enanthate
  • Premarin

Progesterone:

  • medroxyprogesterone acetate
  • norethisterone
  • levonorgestrel
22
Q

HRT routes of administration

A 
Oral - tablet 
Transdermal - patches
Implant 
Transvaginal - pesaries 
Nasal
23
Q

Risk factors of HRT

A

Unopposed oestrogen - increased risk of ovarian and endometrial cancer

Opposed oestrogen - increased risk of breast cancer

Increased risk of DVT - primary oral route

Increased risk of stroke in patients under 60- oral use (tibolone)

24
Q

Active Protein C

A

Inhibits the activation of factor VIII

Inhibits the activation of factor V

25
Q

Antithrombin activity

A

Inhibits the activation of factor X

Inhibits activation of thrombin

26
Q

Protein S

A

Stimulates production of active protein C

27
Q

HRT effects on cardiovascular disease

A

Improves lipid profile as:

  • increases HDL: LDL ratio
  • decreases triglycerides
  • decreased lipoproteins
  • doesn’t occur if the patient is already overweight
28
Q

Mifepristone (RU486)

A

Progesterone (and glucocorticoid) receptor antagonist

  • decreases secretory function of endometrium
  • thin alkaline cervical mucous
  • decreases myometrium contractions - sensitises the myometrium to prostaglandin induced contractions

TERMINATES PREGNANCY

29
Q

SERM

A
  • selective oestrogen receptor modulator

- varied effects in different tissues

30
Q

Examples of SERMs

A

Tamoxifen

Raloxifene - protective against osteoporosis and decreases the acceleration of decreased bone turnover

31
Q

Clomiphene

A
  • treats anovulation
  • competitive oestrogen inhibitor in pituitary gland therefore pituitary perceives a decreased oestrogen environment and released more FSH and LH
  • promotors follicular development and LH surge for ovulation
32
Q

Tamoxifen

A
  • Pro-drug - little affinity for the oestrogen receptor
  • Activated in the liver by first pass metabolism by CYP 450
  • Active metabolites act as competitive inhibitors
  • influenced by epileptics as different isoforms are metabolised by different enzymes
  • Breast:
  • antagonist
  • oestrogen dependent cells do not proliferate therefore decrease risk of breast cancer and slows progression
  • causes cells to arrest in the cell cycle
  • Endometrium - agonist - increased risk of endometrial cancer as the endometrial tissue proliferates
33
Q

Ulipristal acetate

A

Morning after pill

  • selective progesterone receptor modulator
  • inhibits LH surge therefore delays ovulation
  • also treats uterine fibroids

CPT (23 decks)

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