7 - Sex Hormones Flashcards
What are three groups of drugs when considering sex hormones?
Why do drugs based on sex hormones take a while for a response?
They are steroid hormones so act through nuclear receptors so longer response
What are the actions and side effects of oestrogen?
What are the actions and side effects of progesterone?
What are the actions and side effects of testosterone?
What are the different routes of administration for sex steroid hormones?
- Oral
- Transdermal patch
- Implants
- Nasal
- Vagina
How are sex steroids transported in the blood?
- Transport bound to SHBG (except progesterone) and albumin
- SHBG production upregulated by oestrogens – protects against hepatic metabolism
What are some side effects of the combined pill?
- Thromboembolic disease (higher in obese, hypertensives, smokers, long term users and over 35)
- Mood swings
- Decreased glucose tolerance
- Mood swings
- Hypertension
How are sex hormone drugs metabolised and excreted?
- CYP450 in liver
- Metabolites are excreted in faeces and urine as glucuronides and sulphates, respectively
What is the mechanism of action for the COCP and POP?
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
What are some side effects of POP?
In the COCP, which progestins are prescribed?
- Medroxyprogesterone acetate
- Norethisterone
- Levonorgesterel
In the COCP, which oestrogens are prescribed?
ethinylestradiol
How are sex hormones synthesised?
From cholesterol
What drug-drug interactions can occur with the POP and COCP?
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
What advice can one give a female patient who has missed one pill?
- 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
Storage of sex steroid hormones increases half life.
Describe how they are stored.
- Sex steroids easily stored in fatty tissue (adipocytes and brain) as they are lipophilic
- They complex into the plasma membrane just like cholesterol
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)?
- 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
What advice can one give a female patient if there are less than seven pills left in the pack after the last missed pill?
If there are less than seven pills left in the pack after the missed pill – 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
Why is HRT prescribed?
- Helps the symptoms of menopause e.g hot flushes, dyspareunia, genital atrophy
- Helps osteoporosis
- NOT cardioprotective
Identify five types of steroids used in HRT and their dosing regimen
- Oestrogen only: can only be given to a woman without a uterus
- HRT: progesterone given with oestrogen as progesterone has antiproliferative effects on endometrium
What are the side effects/risks of HRT?
- 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
What are the routes of administration for HRT?
- Oral
- Transdermal
- Implant
- Transvaginal
- Nasal
What is the mechanism of action of Mifepristone (RU486) and what class of drug is it?
- Antiprogesterone: Progesterone and glucocorticoid antagonist
- Sensitises the myometrium to prostaglandin induced contraction
- Terminates pregnancy or labour induction
What are anti-androgens used for?
- Cyproterone
- Weak progestogenic effect
- Partial agonist at the progesterone receptor, that competes with dihydrotestosterone
- Used in combined contraceptive pill and can be used to treat advanced prostate cancer
What class of drug is clomiphene and what is it used for?
- 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
What class of drug is Tamoxifen and what is it used for?
- 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
Describe five effects/side effects of selective estrogen receptor modulators.
- 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
What are two emergency contraceptives and what are their mechanisms of action?
- 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
What can SERMs be used for?
- Breast cancer chemotherapy
- Anovulation
- HRT
A man from ethiopia has a deficiency in CYP2D6, what effect would you expect to see if he was using codeine as an analgesic?
Decreased therapeutic effect, need an increase dose as it is a prodrug that needs metabolising to be active
In a patient with hepatic disease, what affect will this have on the therapeutic action of tamoxifen?
Decreased as tamoxifen is a prodrug
What hormones are involed in HRT that increase the risk of breast cancer when used in the short term?
Estradiol plus one of:
- Medroxyprogesterone
- Levonorgesterol
- Dydrogesterone
What are the major effects of oestradiol, progesterone and testosterone??
