7 - Sex Hormones

Question 1

What are three groups of drugs when considering sex hormones?

Answer 1

Question 2

Why do drugs based on sex hormones take a while for a response?

Answer 2

They are steroid hormones so act through nuclear receptors so longer response

Question 3

What are the actions and side effects of oestrogen?

Answer 3

Question 4

What are the actions and side effects of progesterone?

Answer 4

Question 5

What are the actions and side effects of testosterone?

Answer 5

Question 6

What are the different routes of administration for sex steroid hormones?

Answer 6

• Oral
• Transdermal patch
• Implants
• Nasal
• Vagina

Question 7

How are sex steroids transported in the blood?

Answer 7

• Transport bound to SHBG (except progesterone) and albumin
• SHBG production upregulated by oestrogens – protects against hepatic metabolism

Question 8

What are some side effects of the combined pill?

Answer 8

• Thromboembolic disease (higher in obese, hypertensives, smokers, long term users and over 35)
• Mood swings
• Decreased glucose tolerance
• Mood swings
• Hypertension

Question 9

How are sex hormone drugs metabolised and excreted?

Answer 9

• CYP450 in liver
• Metabolites are excreted in faeces and urine as glucuronides and sulphates, respectively

Question 10

What is the mechanism of action for the COCP and POP?

Answer 10

COCP:

• Suppression of ovulation (inhibits FSH, LH)
• Thickens cervical mucus (more viscous)
• Prevents secretory phase in endometrium (remains atrophic)

POP: (low dose)

• Thicken cervical mucous
• Atrophy endometrium
• High dose implant stops ovulation but this doesn’t
• Need constant oestrogen as progestrone receptors only present when oestrogen around so not good if woman producing low oestrogen

Question 11

What are some side effects of POP?

Answer 11

Question 12

In the COCP, which progestins are prescribed?

Answer 12

• Medroxyprogesterone acetate
• Norethisterone
• Levonorgesterel

Question 13

In the COCP, which oestrogens are prescribed?

Answer 13

ethinylestradiol

Question 14

How are sex hormones synthesised?

Answer 14

From cholesterol

Question 15

What drug-drug interactions can occur with the POP and COCP?

Answer 15

Metabolised by CYP450 so the following enzyme inducing drugs can lower the drugs response:

• Antiepileptics like carbamazepine and phenytoin

- Rifampicin and rifabutin

- St John’s Wort

- Soya protein for perimenopausal symptoms can enhance oestrogen absorption and reduce its storage in adipose so half life from 15 to 7 hours

Question 16

What advice can one give a female patient who has missed one pill?

Answer 16

• Take the last pill immediately, even if this means taking two pills in one day
• Continue taking the rest of the pack as normal
• Take seven day pill free break as normal or take (inactive) pills

Question 17

Storage of sex steroid hormones increases half life.

Describe how they are stored.

Answer 17

• Sex steroids easily stored in fatty tissue (adipocytes and brain) as they are lipophilic
• They complex into the plasma membrane just like cholesterol

Question 18

What advice can one give a female patient who has missed two pills anywhere in the pack or started a new pack two or more days late (48 hours or more)?

Answer 18

• Take the last pill immediately, even if this means taking two pills in one day
• Continue taking the rest of the pack as normal
• Use extra contraception for the following seven days

Question 19

What advice can one give a female patient if there are less than seven pills left in the pack after the last missed pill?

Answer 19

Finish the pack and start a new pack the next day; this means missing out the pill-free break or not taking your inactive pills

Question 20

Why is HRT prescribed?

Answer 20

• Helps the symptoms of menopause e.g hot flushes, dyspareunia, genital atrophy
• Helps osteoporosis
• NOT cardioprotective

Question 21

Identify five types of steroids used in HRT and their dosing regimen

Answer 21

- Oestrogen only: can only be given to a woman without a uterus (cause endometrial hyperplasia –> cancer)

- HRT: progesterone given with oestrogen as progesterone has antiproliferative effects on endometrium

Question 22

What are the side effects/risks of HRT?

Answer 22

• Increased chance of breast cancer (mainly HRT)
• Increased risk of endometrial and ovarian cancer in unopposed oestrogen
• Risks of DVT and PE as oestrogen makes you hypercoagulable (only oral)

- Stroke and ischaemic heart disease

Question 23

What are the routes of administration for HRT?

Answer 23

• Oral
• Transdermal
• Implant
• Transvaginal
• Nasal

Question 24

What is the mechanism of action of Mifepristone (RU486) and what class of drug is it?

Answer 24

- Antiprogesterone: Progesterone and glucocorticoid antagonist

• Sensitises the myometrium to prostaglandin induced contraction

- Terminates pregnancy or labour induction

Question 25

What are anti-androgens used for?

Answer 25

**- Cyproterone** - Weak progestogenic effect - **Partial agonist** at the progesterone receptor, that **competes with dihydrotestosterone** - **Used in COCP** and can be used to **treat advanced prostate cancer**

Question 26

What class of drug is clomiphene and what is it used for?

Answer 26

**- SERM:** selective oestrogen receptor modulator - Varying effects depending what tissue it is in - **Induces ovulation** as **prevents oestrogen binding** to receptor on anterior pituitary and having negative feedback so **increased FSH and LH**

Question 27

What class of drug is Tamoxifen and what is it used for?

Answer 27

**- SERM** - _Prodrug_ metabolised in the liver to become active **- Reduces breast cancer** (or risk of) in ER positive cases as binds **ER antagonist** so binds to ER stopping myoepithelial growth - In **endometrium** it acts as **ER agonist** so can **cause menopausal side effects and endometrial cancer**

Question 28

Describe five effects/side effects of selective estrogen receptor modulators (SERM)

Answer 28

- **Protects against osteoporosis** - Oestrogenic effects on bone, lipid metabolism & blood coagulation - No proliferative effects on endometrium & breast - Reduced risk of invasive breast cancer in postmenopausal women with osteoporosis - Increases **hot flushes** (flashes) – sweating

Question 29

What are two emergency contraceptives and what are their mechanisms of action?

Answer 29

**- Levonorgestrel (up to 72 hours):** progestogen. stops ovulation and/or prevents sperm fetilising an egg **- Ulipristal Acetate (up to 120 hours):** selective progesterone receptor modulator. delays or inhibits ovulation and can be used to treat uterine fibroids

Question 30

What can SERMs be used for?

Answer 30

- Breast cancer chemotherapy - Anovulation - HRT

Question 31

A man from ethiopia has a deficiency in CYP2D6, what effect would you expect to see if he was using codeine as an analgesic?

Answer 31

**Decreased therapeutic effect**, need an increase dose as it is a **prodrug** that needs metabolising to be active

Question 32

In a patient with hepatic disease, what affect will this have on the therapeutic action of tamoxifen?

Answer 32

Decreased as tamoxifen is a prodrug

Question 33

What hormones are involed in HRT that increase the risk of breast cancer when used in the short term?

Answer 33

**Estradiol** plus one of: **- Medroxyprogesterone** **- Levonorgesterol** **- Dydrogesterone**

Question 34

What are the major effects of oestradiol, progesterone and testosterone??

Answer 34