Sex Steroids Flashcards
What are sex steroids derived from?
Cholesterol
How broadly do sex steroids work?
Broadly the steroid binds the nuclear receptor which then dissociates from heat shock proteins and alters the rate of transcription of certain genes.
What are the effects and ADRs of oestradiol?
Stimulates growth of endometrium and breast
Stimulates production of progesterone receptor
Mild anabolic
Raises HDL and lowers LDL
Decreased bone resorption
ADRs:
Sodium and water retention Impaired glucose tolerance Increases coagulability – thromboembolism Breast tenderness Nausea and vomiting Hypertension Endometrial hyperplasia and cancer Ovarian metaplasia and cancer Breast hyperplasia and cancer
What are the effects and ADRs of progesterone?
Stimulates growth & secretory phase of the endometrium and growth of breast tissue
Maintains pregnancy
Inhibits production of oestrogen receptor
Anabolic
Increases bone mineral density
ADRs:
weight gain, nausea and vomiting, depression, PMS, lack of concentration, fluid retention, acne
What are the effects and ADRs of testosterone?
Stimulates male characteristics – hirsutism, deep voice, anabolism, aggression
ADRS:
Adverse effect on lipid profile (HDL:LDL ratio), increased risk of atherosclerotic disease
What are uses of oestrogen antagonists?
o Clomiphene – induces ovulation by binding the oestrogen receptor in the anterior pituitary, inhibits negative feedback and increases levels of FSH and LH
o Tamoxifen – reduces the risk of breast cancer by binding to the oestrogen receptor in breast tissue and blocking myoepithelial cell division stimulated by oestrogen. Also
What are uses of anti-progestins?
o Mifepristone – partial agonist of progesterone receptor which inhibits the action progesterone. It sensitises the uterus to prostaglandins which is used for medical termination of pregnancy and to induce labour
What is finasteride? Effect on PSA?
• Androgen replacement therapy – testosterone given as an implant, IM or oral
o Finasteride – prevents hair loss (male pattern baldness) and treats benign prostatic hyperplasia
Reduces PSA by half
How are sex steroid hormones regulated in the menstrual cycle and pregnancy?
- GnRH stimulates pulsatile release of FSH and LH
- FSH is released from the anterior pituitary, stimulated follicles to develop
- The follicle releases oestrogen – causes proliferation of the endometrium
- Unopposed oestrogen leads to a surge in FSH and LH production in the anterior pituitary leading to ovulation (positive feedback)
- The corpus luteum then produces progesterone and oestrogen, maintaining the endometrium for implantation (negative feedback on LH and FSH
- If pregnancy doesn’t occur the corpus luteum stops producing progesterone and oestrogen and the endometrial lining is shed (day one of the cycle)
In pregnancy
• Progesterone maintains the endometrium – produced by the corpus luteum then the placenta
How can the COCP be administered?
- Monophasic – all the tablets contain a fixed amount of oestrogen and progestin
- Biphasic – same amount of oestrogen all the way through, more progestin in the second half of the cycle
- Triphasic – progestin increases in three phases, oestrogen may be fixed or variable
What is the MOA of the COCP?
- Inhibit ovulation by inhibiting the production of FSH and LH
- Make cervical mucous more viscous
- Preventing the secretory phase of the endometrium which remains atrophic
ADRs of COCP?
- Venous thromboembolism
- Myocardial infarction
- Hypertension
- Impaired glucose tolerance
- Stroke (in women with focal migraines)
- Headache
- Mood swings
- Cholestatic jaundice
- Gallstones
- Porphyria
What are some POPs? How do they work?
Progestin-only-pill (mini-pill). Progestins include levonorgestrel, norethisterone, ethynodiol diacetate and desogestrel.
They work by thickening cervical mucus and preventing proliferation of the endometrium.
What is emergency contraception and how does it work?
- Levonorgestrel can be used up to 72 hours post coitus – high dose prevents ovulation, thickens cervical mucus, prevents implantation
- Ulipristal acetate can be used up to 120 hours post coitus – is it a selective progesterone receptor modulator which inhibits ovulation
- The Copper IUD can be used up to 120 hours post coitus – it prevents the blastocyst from implanting by making the endometrium less favourable
What are DDIs of the COCP?
• Inducers of CYP450 can lead to contraceptive failure:
o Phenytoin
o Carbamazepine
o Rifampicin
o St John’s Wort
• Soya products enhance oestrogen absorption and reduce storage in adipose and muscle, reducing the half-life.
