Sex steroid hormones in contraception Flashcards
Progesterone
- Prepares endometrium for implantation
- promotes growth of mammary glands
- a feedback inhibitor for FSH and LH
what r the different sex steroid hormones?
Oestrogens, progestagens, androgens
what r the major effects of:
Oestradiol, Progesterone,Testosterone
what r sex steriod synthesised from?
cholesterol
Oestrogen action and side effects
Progesterone / progestin action and side effects
Testosterone
action and side effects
what r some Routes of Administration?
VINTO
- Oral
- Transdermal patch (Evra®) norelgestromin
- Implants
- Nasal
- Vaginal
how r sex hormones transported and metabolised?
bound to (SHBG: sex hormone binding globule) EXCEPT PROGESTERONE! & also bound to albumin
Liver metabolism: note progesterone almost totally metabolised in one passage through liver
why can liver metabolism of sex steroids be a problem sometimes?
bc can be affected by other drugs that work through the same enzyme that metabolise progesterones!
how r sex steroids stored? elimination rate? excreted?
Sex steroids easily stored in fatty tissue (adipocytes and brain) because they are lipophilic; they r embedded into the plasma membrane just like cholesterol.
SLOW
Metabolites excreted in faeces and urine (as glucuronides and sulphates, respectively)
what type of pills do oral contraceptives exist as?
Exist as 2 types
– Oestrogen + progestin* (COCP)
• Administered in 3 ways
– Progestin only (POP)
• Administered in lots of ways
what r the 3 ways combined (COCP) Oestrogen + progestin r administered?
u don’t need to know details of this
what r the Synthetic derivatives of estrogen?
ethinylestradiol, methoxy derivative (mestranol), valerate
mu ila u know this
what does NICE recommend in terms of dosage for the Combined Oral Contraceptive Pill ?
lowest dose possible)
Mode of Action of COCP (3 effects of oral contraceptives)
§ Suppression of ovulation: inhibits FSH, LH
§ cervical mucus – makes it more viscous
§ Adverse effect on the endometrium– endometerium doesnt grow as much>> prevent implantation
complications of oral contraceptives
Adverse Effects of COCP
make mneumonc
those women who develop hypertension from COCP, what can be done?
swap them from the combined pill to progesterone only pill!
in what case is the COCP’s efficacy reduced?
- Metabolised by cytochrome P450 (hepatic)>> [Take home message]
- COCP’s efficacy therefore reduced by enzyme inducing drugs
– anti-epileptics such as carbamazepine or phenytoin;
– some antibiotics such as rifampicin & rifabutin
– some natural products such St John’s Wort
• because they all increase the production of hepatic P450
Missed Pill Advice (what is a missed pill?)
if 2 Two missed pills ?
why is soy bad for u?
Soycontains phytoestrogens called isoflavones that may mimic the activity of the hormone estrogen in your body.
Soya protein products enhance oestrogen (EE) absorption and reduce its storage in adipose and muscle and so cause the T1/2 to be reduced from ~15 to 7 hours
what 3 ways r progesterone given?
Mode of Action of POPs Mini-pill / “progestin-only pill”
Work by effecting the cervical mucous and the endometrium
when does POP work best?
Work best when started in the follicular phase of the menstrual cycle.
what r other ways of administering progesitns?
Medroxy Progesterone Acetate (MPA)
§ Depot Provera® MPA
given every 12 weeks
“
”…works by releasing progestin slowly into the body, suppressing oestrogen and other hormone levels. This thickens mucus from the neck of the womb and makes the lining of the womb thinner as well as preventing the ovaries from releasing an egg…”*
when giving a progestin pill, why must the oestrogen be supplied either continuously or prior to the progestin?
for the drugs to work, receptor needs to be present and because progesterone receptor expression is dependent upon oestrogen action, the oestrogen must be supplied either continuously or prior to the progestin.
Emergency contraception
Understand why sex steroid hormone derivatives should be given for the
menopause?
In postmenopausal women, main indication is hot flushes/vaginal dryness
Why prescribe HRT?
- releive menopause symptoms: hot flushes/sweats, vaginal dryness, dyspareunia
- Osteoporosis
X Heart disease >> but gives adverse effects in those w/ heart disease!!
Osteoporosis causes bones to become less dense and more fragile (we have normal bone, but not enough of it), it is a process that involves the degeneration of already contructed bone!
Mode of action of sex steroids on HRT?
slow release agonist that replicates the action of natural hormone
how is combined HRT given?
estrogen & Progestin
28 days of either estrogen only & then combined
or continuously combined!
major risky side effects and ADR of hormone replacement therapy (HRT) & ERT
- Unopposed oestrogen (estrogen ONLY) (ERT): increases risk of developing endometrial & ovarian cancers
- Opposed oestrogen (HRT): increases risk of developing breast cancer & thromboembolism
- Increased risk of stroke and ischaemic heart disease
- Increase risk of venous thromboembolism
benefits of HRT
weirdly, it does have a beneficial effect on lipid profile> it increases HDL, decreases OxLDL, decreases TAG, decreases lipoprotein(a)*
bs despite all of that,….it doesn’t seem to have a benifical effect on reducing risk of IHD
what is HRT adverse effect on thromboembolism profile?
routes of administration of HRT?
ORAL
TRANSDERMAL
IMPLANT
TRANSVAGINAL
NASAL
Role of anti-estrogens
(name 2)
§ Clomiphene: ovulation induction
- Inhibits oestrogen binding to its ER in the anterior pituitary
- Inhibits negative feedback
- Results in increased FSH, LH expression
§ Tamoxifen: reduces risk of breast cancer
- Binds to ER in breast tissue & blocks oestrogen-stimulated myoepithelial cell division
- Also causes ovulation induction
Role of anti-progestogens
role of Anti-androgens
role of SERMS
(what does it stand for)
why do Androgen Replacement Therapy ?
- those who wanna transgender
- or if men just have low testosterone levels
action of Finasteride? effects? why is it not approved for pregnant women?
FinAsteride >> five alpha reductase inhbitor
negative effect on 5-alpha reductase> which normally pushes testosterone to 5a diy..bla bla
baba loves finaster!
Remember: for the drugs to work, receptor needs to be present and because progesterone receptor expression is dependent upon oestrogen action
………. the oestrogen must be supplied either continuously or prior to the progestin.
what drugs can interact w/ the combined oral contracpetive pill to reduce its efficiacy?
anti-epileptics-carbamazepin/phneytoin
antiobiotics- rimfampicin, rifabutin
natural products-st Johns wort
Role of Progesterone at moderate/high doses & low doses
