S5) Sex Hormones Flashcards
Identify three drug groups of consideration when considering sex hormones
- Sex steroid hormones
- Inhibitors and antagonists
- Mixed agonists / antagonists
What are the major effects of oestradiol?
- Stimulates growth of the endometrium and breast
- Stimulates production of PR
What are the major effects of progesterone?
- Stimulates growth of the endometrium and breast
- Maintains pregnancy
- Inhibits production of ER
What are the major effects of testosterone?
Stimulates male characteristics – hairy body, deep voice, anabolism, aggression
Identify five effects of oestrogen
- Sodium and water retention
- ↑ HDL, ↓ LDL
- Decrease bone resorption
- Impair glucose tolerance
- Increase blood coagulability
Identify five side effects of oestrogen
- Breast tenderness
- Nausea & vomiting
- Water retention
- Increased blood coagulability
- Thromboembolism
Identify five effects of progesterone
- Secretory endometrium
- Increases bone mineral density
- Fluid retention
- Mood changes
- Maintains pregnancy
Identify five side effects of progesterone
- Weight gain
- Fluid retention
- Acne
- Nausea/vomiting
- Irritability
Identify four effects / side effects of testosterone
- Male secondary sex characteristics
- Acne
- Voice changes
- Increases aggression
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
Sex steroid hormones are metabolised in the liver.
Explain how this occurs for progesterone
Liver metabolism – progesterone almost totally metabolised in one passage through liver
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
How are sex steroid hormones excreted?
Metabolites are excreted in faeces and urine as glucuronides and sulphates, respectively
Sex steroids are effective by binding to nuclear receptors.
Which receptors are used by the following sex steroid hormones:
- Oestrogens
- Progestagens
- Androgens
- Oestrogens – ERα and ERβ
- Progestagens – PR-A and PR-B
- Androgens – AR-1 and AR-2
In the COCP, which oestrogens are prescribed and what are their half lives?
- Ethinylestradiol (T1/2 ~ 15 hours)
- Mestranol (T1/2 8-24 hours)
In the COCP, which progestins are prescribed?
- Levonorgestrel
- Norethisterone
- Desogestrel
What is the mode of action of the COCP?
- Suppression of ovulation (inhibits FSH, LH)
- Thickens cervical mucus (more viscous)
- Prevents secretory phase in endometrium (remains atrophic)
Identify five adverse effects of the COCP
- Venous thromboembolism
- Myocardial infarction
- Hypertension
- Decrease glucose tolerance
- Mood swings
What is the mode of action of the progestin only pill?
- Thicken cervical mucous
- Atrophy endometrium
How can the management for missed pill advice change?
Management depends on:
- How many pills have been missed (a missed pill is when it’s more than 24 hours)
- When the pill was missed (time in pack)
- The type of combined pill
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
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 seven or more pills left in the pack after the last missed pill?
If there are seven or more pills left in the pack after the last missed pill – finish the pack and take seven-day pill-free break as normal or, take (inactive) pills
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
Which emergency contraception can be provided up to 72 hours post coitus?
Up to 72 hours post coitus – Levonorgestrel 1.5mg
Which emergency contraception can be provided up to 120 hours post coitus?
- Ullipristal acetate 30mg – selective progesterone receptor modulator
- Cu2+ IUD – prevents blastocyst attachment to endometrium
Identify two types of hormonal regimes
- Oestrogen replacement therapy (ERT)
- Hormone replacement therapy (HRT)
What are the indications for HRT?
- Symptoms: hot flushes, sweats, vaginal dryness, dyspareunia
- Osteoporosis
What are the contraindications for HRT?
Heart disease
Identify five types of steroids used in HRT and their dosing regimen
- Oestradiol (1-2 mg/day)
- Medroxyprogesterone acetate (2.5 mg/day)
- Norethisterone (1 mg/day)
- Levonorgestrel (1.5 mg/day)
What are the routes of administration for HRT?
- Oral
- Transdermal
- Implant
- Transvaginal
- Nasal
What are the risks of HRT?
- Unopposed oestrogen (ERT) – increases risk of developing endometrial and ovarian cancers
- Opposed oestrogen (HRT) – increases risk of developing breast cancer
- Increased risk of stroke and ischaemic heart disease
- Increase risk of venous thromboembolism
In terms of sex hormones, what are inhibitors/oestrogens?
Inhibitors/oestrogens are weak oestrogens that block receptors
The inhibitor/antagonist, clomiphene, acts by ovulation induction.
Explain how this occurs as well as its result
- Inhibits oestrogen binding to its ER in the anterior pituitary
- Inhibits negative feedback
- Results in increased FSH, LH expression
The inhibitor/antagonist, tamoxifen reduces risk of breast cancer.
Explain how this occurs
- Binds to ER in breast tissue and blocks oestrogen-stimulated myoepithelial cell division
- Causes ovulation induction
The inhibitor/antagonist, mifepristone (RU486) is an anti-progestin.
Explain its mechanism of action and its uses.
- Partial agonist to progesterone receptor, inhibits progesterone action
- Sensitises the uterus to prostaglandins
- Used for medical termination of pregnancy and induction of labour
The inhibitor/antagonist, cyproterone is an anti-androgen.
Describe its mechanism of action and uses
- 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
How can androgen replacement therapy be administered?
- Implants e.g. Testosterone
- Intramuscular e.g. Enenthate, Proprionate
- Oral e.g. Undecanoate, Mesterolone
Describe the effects of finasteride?
- Prevents hair loss
- Male pattern baldness
- Benign prostatic hyperplasia
What is a contraindication of finasteride?
Finasteride is not approved for use in women, especially due to risks of birth defects in a foetus
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
