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Clinical Pharmacology and Therapeutics > Sex Steroid Hormones, Oral Contraceptives, and HRT > Flashcards

Sex Steroid Hormones, Oral Contraceptives, and HRT Flashcards

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1
Q

What % of sex steroid hormones are bound to SHBG and albumin?

A

98%

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2
Q

Why are they bound to SHBG?

A

To protect against liver metabolism of free hormones

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3
Q

What causes SHBG to be produced?

A

Oestrogens upregulate SHBG production

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4
Q

Where are sex steroids stored within the body and why?

A

Within fatty tissue as they are lipophilic

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5
Q

How are sex stroid metabolites excreted?

A

In faeces as glucuronide, and urine as sulphates

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6
Q

What are the oestrogen receptors in the body?

A

ERα and ERβ

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7
Q

Apart from ERα and ERβ, are there other oestorgen receptors?

A

Not in normal physiology, but there can be in cancer

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8
Q

What are the progesterone receptors in the body?

A

PR-A and PR-B

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9
Q

What are the androgen receptors in the body?

A

AR-1 and AR-2

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10
Q

Where do AR-1 receptors exist within the body?

A

Testes, penis, and prostate

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11
Q

Where do AR-2 receptors exist within the body?

A

Liver, bone, and hair follicles

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12
Q

What happens when oestrogen binds to an oestrogen receptor?

A

Oestrogen response element responds to stimulus by starting processes like transcription. Response is regulated by co-factors and integrators.

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13
Q

In terms of the response to oestrogen, how do cofactors and integrators act?

A

Co-factors act to stabilise the process so more transcription takes place.

Integrator are mainly negative in action.

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14
Q

Why are oestrogen receptors alpha and beta, but androgen and progesterone A&B/1&2?

A

ERs are generated from different genes on different chromosomes, but ARs and PRs are isoforms generated from alternate splicing of genes

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15
Q

When does steroid receptor expression vary?

A

Throughout the menstrual cycle

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16
Q

When in the menstrual cycle are more ER alpha receptors expressed?

A

Proliferative phase

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17
Q

When in the menstrual cycle are more ER beta receptors expressed?

A

Secretory phase

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18
Q

When in the menstrual cycle are more AR receptors expressed?

A

Late secretory phase

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19
Q

When in the menstrual cycle are more PR receptors expressed?

A

More in glands in proliferative phase, but more in stroma in secretory phase

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20
Q

What are synthetic progestagens called?

A

Progestins

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21
Q

What drug classes can we use to target steroid hormone receptors?

A
  • Natural/synthetic sex steroid hormones i.e. agonists
  • Inhibitors and Antagonists
  • Mixed agonists/antagonists
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22
Q

Name some examples of inhibitors and antagonists of steroid hormone receptors.

A

Clomiphene
Finesteride
RU 486

Actually these are all partial agonists, technically speaking.

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23
Q

Name some examples of mixed agonist/antagonists of steroid hormone receptors.

A

SERMs (selective oestrogen receptor modulators)
SPRMs
SARMs

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24
Q

What is the major effect of oestradiol in the body?

A

Stimulates endometrial and breast growth, and progesterone receptor production.

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25
What is the major effect of progesterone in the body?
Stimulates endometrial and breast growth, and inhibits oestrogen receptor production. Maintains pregnancy.
26
What is the major effect of testosterone in the body?
Stimulates male characteristics (hair, voice, anabolism, agression).
27
What are sex steroid hormones synthesised from?
Cholesterol
28
Where does sex steroid hormone production occur?
Adrenal gland, adipose tissue, and gonads.
29
What are the 3 main endogenous oestrogens?
Estradiol Estrone Estriol
30
Which oestrogen is at high levels during pregnancy? Why is tis useful?
Estriol - we can use it as a marker for good pregnancy progression.
31
What can we use progesterone derivatives for?
Delaying the onset of labour to prevent preterm birth
32
What is the most commonly presecribed testosterone derivative, and what are they for?
``` Levonogestrel = morning after pill Desogestrel = POP Norgestrel = OCP ```
33
Aside form its action in the menstrual cycle, what other effects does oestrogen have on the body?
``` Mild anabolic effect Na2+ and water retention HDL increase, LDL decrease Decreases bone resorption Impairs glucose tolerance Increases blood coagulability ```
34
What side effects can oestrogen cause?
``` Breast tenderness N&V Water retention Increases blood coagulability Thromboembolism Impairs glucose tolerance ```
35
Aside form its action in the menstrual cycle, what other effects does progesterone have on the body?
Anabolic Fluid retention Increase bone mineral density Mood changes
36
What side effects can progesterone cause?
``` Weigh gain Fluid retention Acne Anabolic N&V Irritability PMS Depression Lack of concentration ```
37
What metabolic effect does testosterone have, and why is this important?
Adverse effect on HDL/LDL ratio so there is a higher risk of atherosclerotic disease in males and gender-reassigned females
38
What are the 2 types of OCPs?
COCP | POP
39
What 3 types of COCP are there?
Monophasic Biphasic Triphasic
40
Tell me about monophasic, biphasic, and triphasic COCPs.
Monophasic - every tablet has the same amount of O and P. Biphasic - every tablet has the same amount of O, but P increased for second half of cycle. Triphhasic - O fixed then variable, P increases in 3 equal phases.
41
How are oestrogens reccommended to be started?
At lowest dose, and if that is ineffective, increase the dose.
42
How does the COCP work?
Suppresses ovulation by inhibiting FSH and LH. Increased viscosity of cervical mucus. Prevents secretory phase of endometrium (remains atrophic).
43
What are the risks associted with COCP?
``` VTE MI HTN Impaired glucose tolerance Stroke in women with focal migraines Headaches Mood swings Cholestatic jaundice Gallstones ```
44
What is important about oestrogen and progesterone metabolism wrt COCP?
It is metabolised by CP450 in the liver so may become ineffective if inducers are taken alongside COCP.
45
Tell me about the POP.
28 days of progestin (different forms). | Works best if started at begining of follicular phase/start of menstrual bleed.
46
What is the depot?
Medroxy progesterone acetate | Given every 12 weeks
47
What is Nexplanon?
A brand of etonogestrel used as the implant in females as contraception.
48
What are the 3 kinds of emergency contraception?
Levonogestrel Ulipristal acetate (EllaOne) Cu2+ IUD
49
What is ulipristal acetate and how does it work?
SPRM - suprresses LH surge and prevents ovulation.
50
When can EllaOne be taken?
Up to 120 hours post-coitus
51
When can levonogestrel be taken?
Up to 72 hours post-coitus
52
How does the Cu2+ IUD work?
Copper is toxic to the blastocyst, acts as a spermicide, and prevents endometrial attachment by altering the uterine and tubal environment.
53
What is HRT/ORT prescribed for?
Symptoms of hot flushes, vaginal dryness, or if the pt is at risk of developing osteoporosis.
54
Who is HRT contraindicated in?
Anyone with heart disease
55
How can HRT be administered?
``` Oral Transdermal Implant Transvaginal Nasal ```
56
Which agents are used in HRT?
Oestradiol or Premarin | +/- medroxyprogesterone acetate/Norethisterone/Levonorgestrel
57
What are the risks of HRT?
Unopposed oestrogen in ERT increases risk of developing endometrial/ovarian cancer. Opposed oestrogen in HRT increases risk of developing breast cancer. Increased risk of VTE and stroke
58
What are the benefits of HRT/ERT (aside from the aim of treatment)?
Beneficial effect on risk of IHD, as well as higher HDL, lower LDL, TAG and lipoproteins.
59
What does clomiphene do?
Weak oestrogen/partial agonist: - Induces ovulation - Inhibits Oestrogen binding in anterior pituitary so LH and FSH expression increases
60
What is clomphene used for?
Female infertility
61
What does tamoxifen do?
Weak oestrogen/partial agonist: - Reduces risk of breast cancer in ER positive women by blocking receptor to prevent cell division. - Induces ovulation
62
Tell me about antiprogestins.
Partial PR agonists to prevent progesterone action. Sensitises uterus to prostaglandins.
63
What are antiprogestins used for?
Medical termination of pregnancy | Induction of labour
64
What is Mifepristone (RU 486)?
Antiprogestin
65
Tell me about antiandrogens.
Progesterone derivatives that compete with dihydrotestosterone.
66
What is finasteride?
5 alpha reductase inhibitor used for BPH and androgenetic alopecia in men
67
What is the main SERM?
Raloxifene
68
What is raloxifene used for?
- Post-menopausal osteoporosis (Rx and Prevention) | - Breast cancer chemoprevention
69
How does raloxifene work?
Oestrogenic effect on bone, lipid metabolism, and coagulation.

Clinical Pharmacology and Therapeutics (26 decks)

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