hormonal contraception Flashcards
hypothalamus producing GnRH
produces it in a cyclical manner
GnRH acts on
anterior pituitary to make it produce FSH and LH
HPO axis
hypothalamo-pituitary-ovarian
FSH acts during
first half of the manstual cycle
LH acts during
2nd half of the menstrual cycle
FSH causes production of
oestrogen from granuloma cells in dominant follicle
LH causes production of
porgesterone>oestrogen
3 endogenous oestrogenen
E2 - 17b oestradiol, major
E1 - estrone, minor
E3 - oestriol, pregnancy
17b oestradiol E2
most abundant and potent
produced by ovarian granulosa cells
oestrone E1
produced by ovaries and adrenals
levels increase slightly after menopause
oestriol E3
placental - only in pregnancy
endogenous oestrogens are
18-carbon steroids
transported by SHBG
bind oestrogen receptors
oestrogen receptors
ERa and ERb
expressed redundantly in reproductive system and breast
expressed non-redundantly in CVS, skeleton, CNS and immune system - not reproductive effects of oral contraceptives
ERa/b are ligand activated transcription factors (target genes with EREs) - slow response time
ERa over expressed in
breast cancers
not ERb
anti oestrogen blocking ERa are widely used in breast cancer
oestrogen levels modulate
FSH and LH release
cyclical changes in uterus and breasts
induction of progesterone receptors
metabolic actions of oestrogen
increase bone mass by blocking bone resorption - why women are more susceptible to osteoporosis
improve TG profile - improve HDL:LDL ratio
increase coagulability - venous thrombosis embolism and stroke
progesterone
secreted mainly by the corpus luteum and placenta
secreted in the second half of the cycle
levels decrease before mestruation (unless pregnant)
transported by albumin and corticosteroid binding globulin CBG
progesterone receptor
ligand activated transcription factor expressed in female reproductive tract, breast and CNS
actions of progesterone
prepare for/maintain pregnancy
uterine/cervical effects
- endometrium, decreased proliferation, increase secretory changes
- cervix - thickens and decrease secretions, decrease sperm penetration
- myometrium - decrease uterine excitability
- breasts - glandular development
- hypothalamus - decrease LH surge and GnRH release, block ovulation
- CNS - increase body temperature
2 types oral contraceptives
- combined contraceptives (COCs) contain oestrogen and a progestogen
- progestogen only contraceptives
until recently, endogenous hormones were not used orally due to
their extensive 1st pass hepatic metabolic - very low bioavailability
combined oral contraceptives
contain a synthetic oestrogen and a synthetic progestogen
oestrogens used in the pilll
ethinyloestradiol and mestranol
synthetic oestrogens
ethinylestradiol EE- derivative of estradiol, addition of ethinyl group to reduce hepatic metabolism and allow it to be taken orally
mestranol - pro-drug of EE - undergoes demethylation, less potent
synthetic progestogens
multiple - differentiations in potency and spectrum of activity
1st generation - ethisterone - significant androgenic effects: acne, hirsutism, weight gain, no longer used
2nd generation - norethisterone, levonorgestrel - reduced androgenic side effects
3rd generation - desogestrel, gestodene - reduced androgenic and lipid effects but increased thromboembolic effects
how does the combined pill work
inhibit ovulation - prevent release of FSH (follicle development) and LH (ovulation
synergistic effect of oestrogen (FSH) and progestogen (LH)
thickens cervical mucus - forms a barrier to sperm via progestogen effect
thin endometrial lining - reduce endometrial receptivity to inhibit implantation
3 mechanisms of combined pill
inhibit ovulation
thicken cervical mucus
thin endometrial lining
efficacy of COC
> 99% with perfect use
effectiveness reduced by
- compliance
- delayed start of the next pack - decrease HPO suppression
- missed pills
- vomiting - decreases intestinal absorption
- broad spectrum antibiotics (ampicillin) - decreases enterohepatic circulation (probably more a theoretical than a real problem)
- CYP3A4 induction - griseofulvin, anti-epileptics (phenytoin, carbamazepine), TB drugs (rifampicin), st john’s wort
regimens and dose of COC
21 days OC and 7 days placebo
7 days hormone free - withdrawal bleed (not a period)
no biological reason for a withdrawal bleed and extended OCP regimens may increase compliance
COC formulations
monophasic - same daily dose of EE and progestogen phased regimens (biphasic and triphasic) - dose varies to mimic cyclical endogenous hormone secretion biphasic - constant EE, progestogen in 2nd half of cycle triphasic - increase EE in middle to decrease breakthrough bleeding plus stepwise increase in progesterone no contraceptive advantage
breakthrough bleeding
treat by increasing oestrogen or progesterone
nausea
treat by reducing oestrogen dose to take the pill at night with food
fluid retention, breast tenderness
treat by decreasing oestrogen dose
chloasma
treat by avoiding sun, use sun screen
androgenic and antiandrogenic side effects
ance
depression, irritability and fatigue
reduction in libido
enhanced coagulation
dose related risk
metabolic side effect of oestrogen
older contraceptives had more of a problem with this
increases clotting - DVT, pulmonary embolism, MC, stroke
increase risk in obesity, long haul travel and underlying genetic clotting abnormalities eg. factor 5 laden
MI risk increases >35yo, smoker, hypertensive
breast cancer and oestrogen
oestrogen promotes breast cancer - early menarche, nulliparity, late age of 1st pregnancy, lack of breast feeding - all increases risk of breast cancer
role of progestogen is more complex
increased risk of breast cancer in usage of the pill
reduction in risk when pill is stopped
cervical cancer risk
causal link not established
may be behavioural in origin - OC users more sexually active, use barrier contraceptive methods less, exposed to HPV
protective risk effects of COC
decreased ovarian risk, endometrial, colorectal
decreased risk os long term - does not diminish when pill is ceased
reduced risk of PID, salpingitis and ectopic pregnancy
improvement in acne
improvement in menstrual problems: cramps, heavy flow, endometriosis, premenstual syndrome, iron deficiency anaemia
contraindications of the COC
- pregnancy
- history of VTE or Stroke
- CVD - coronary artery disease, valvular disease
- major elective surgery - stop 1 month beforehand
- oestrogen dependant breast cancer sufferer
- migraine with aura - increase stroke risk
- hepatic disease - acute hepatitis, severe cirrhosis
>35 years old, obese, smoker with HT and DM
progestogen only OC
minipill
contain no oestrogen
useful with COC is contraindicated or not tolerated
progestogen only OC mechanism of action
- inhibitor of ovulation due to inhibition of LH surge
- thickens and decreases amount of servical mucous, impedes sperm penetration
- endometrium thins - decreases implantation rate
30-40% of progestogen only OCs still ovulate, so less effective than combined OCs
requires more meticulous compliance
minipill
progestogen only OC
long acting reversible contraceptives
LARCs
IUDs, progestogen implants
more effective reversible contraceptive
20x more effective than OC
safe for most women, including adolescents, post partum, post abortion
menstrual cycle disturbance is common, with irregular bleeding but decreased bleeding over time
levonorgestrel IUD often decreases bleeding - used therapeutically
antisperm antibodies
some women naturally produce antibodies to sperm
immunological infertility
topically delivered trap >99.9% of sperm
still in clinical trials
