combined oral contraceptive pill (OCP)
1st generation OCPs
based on norethisterone as the progestogen, or norethindrone (NE), ethynodiol diacetate, or lynestrenol (LYN).
norethisterone 0.5mg with ethinyloestradiol 35mcg
biphasic norethisterone with ethinyloestradiol 35mcg
norethisterone 500 mcg, ethinyloestradiol 35 mcg (12 blue tabs: days 1-7 and 17-21); norethisterone 1 mg, ethinyloestradiol 35 mcg (9 white tabs: days 8-16); inactive: (7 orange tabs: days 22-28)
Synphasic 28, Improvil 28
norethisterone 1mg with ethinyloestradiol 35mcg
2nd generation OCPs
based on levonorgestrel as the progestogen which was introduced to the market in the 1970's
reduced discontinuation rates compared to 1st generation OCP's (RR 0.79 (95% confidence interval [CI]: 0.69–0.91))
improved cycle control comapred to 1st generation OCP's
similar rates for contraceptive effectiveness, spotting, breakthrough bleeding and the absence of withdrawal bleeding compared to gestodene based OCP's, but more intermenstrual bleeding than with gestodene
3)
half the risk of
deep venous thrombosis (DVT) compared to 3rd generation OCP's containing the progestogens desogestrel, gestodene, cyproterone, or drospirenone
4)
higher pregnancy rates with OCP's containing only 20mcg ethinyloestradiol
levonorgestrel 100mcg with ethinyloestradiol 20mcg
lowest oestrogen dose and thus likely to have the least side effects other than menstrual, but the highest pregnancy rates
may be suitable to help those with acne but needs strict compliance
eg. Microgynon 20, Loette, Microlevlen ED
triphasic levonorgestrel with ethinyloestradiol
progesterone dose increases throughout cycle while oestrogen dose peaks mid-cycle
Triquilar ED, Logynon ED:
levonorgestrel 50 mcg, ethinyloestradiol 30 mcg (6 brown coated); levonorgestrel 75 mcg, ethinyloestradiol 40 mcg (5 white coated); levonorgestrel 125 mcg, ethinyloestradiol 30 mcg (10 ochre coated); inactive (7 larger white); lactose, sucrose;
Triphasil ED, Trifeme:
levonorgestrel 50 mcg, ethinyloestradiol 30 mcg (6 brown tabs); levonorgestrel 75 mcg, ethinyloestradiol 40 mcg (5 white tabs); levonorgestrel 125 mcg, ethinyloestradiol 30 mcg (10 yellow tabs); inactive (7 red tabs); lactose, sucrose
levonorgestrel 150mcg with ethinyloestradiol 30mcg
levonorgestrel 150mcg with ethinyloestradiol 50mcg
high oestrogen dose pill
eg. Microgynon 50 ED
anti-androgenic OCP's
cyproterone is a synthetic steroidal antiandrogen drug with additional weak progestogen and antigonadotropic properties
Dienogest is a semisynthetic, steroidal progestogen with antiandrogenic activity
suitable for those with acne and hirsutism
Combined oral contraceptives containing the progestogens desogestrel, gestodene, cyproterone, or drospirenone confer about the same relative risk of venous thromboembolism, a risk that is about twice that from use of combined oral contraceptives with the same dose of oestrogen and levonorgestrel.
6)
drospirenone 3mg with ethinyloestradiol 20mcg
cyproterone 2mg with ethinyloestradiol 35mcg
eg. Diane-35, Carolyn-35, Estelle-35, Juliet-35, Laila-35, Brenda-35
cyclic adapted dienogest with oestradiol
3rd generation OCPs:
containing 1 of 3 new progestins:
norgestimate 0.2mg
desogestrel 0.06mg
gestodene 0.04mg
may have increased thrombogenic adverse effects, particularly with ethinyl-oestradiol doses of 30-40mcg
users of oral contraceptives with desogestrel, gestodene, or drospirenone were at least at twice the risk of venous thromboembolism compared with users of oral contraceptives with levonorgestrel.
7)
desogestrel 150 mcg with ethinyloestradiol 30 mcg
higher risk of thrombotic stroke (RR 2.2 (1.8-2.7)) or
AMI (RR 2.1 (1.5-2.8))
8)
eg. Marvelon 28
eg. Gedarel 30/150
gestodene 75 mcg with ethinyloestradiol 30 mcg
moderately higher risk of thrombotic stroke (RR 1.8 (1.6-2.0)) or
AMI (RR 1.9 (1.6-2.3))
9)
eg. Femoden ED
nomegestrol with endogenous 17B-oestradiol
mechanism of action:
primary action:
prevention of ovulation:
inhibits follicular development, ovulation, and, as a consequence, corpus luteum formation
this is reflected in a marked reduction of ovarian estradiol secretion and the absence of progesterone production
mechanism is via hypothalamic inhibition of GnRH secretion & thus inhibition of LH & FSH secretion:
either oestrogen or progestin alone is capable of inhibiting FSH and LH sufficiently to prevent ovulation. However, the combined administration of both compounds greatly increases their antigonadotropic and ovulation-inhibition effects
the progestin component of combined oral contraceptives is particularly effective in terms of ovulation inhibition, given its ability to block the midcycle rise in LH secretion
ethinyl estradiol in combined oral contraceptives potentiates the antigonadotropic effect of the progestin and prevents irregular shedding of the endometrium.
it has also been reported that important individual and ethnic differences in the biologic effects and metabolism of synthetic estrogens and progestins exist, which may also influence their contraceptive action.
the effect of combined oral contraceptives on FSH and LH secretion is prompt, lowering circulating FSH and LH levels within the first day of administration. However, at least 7 days of uninterrupted daily use of combined oral contraceptives is necessary to suppress follicular development.
combined oral contraceptives are administered for a 21-day cycle followed by a 7-day pill-free cycle, to mimic a 28-day menstrual cycle. FSH and LH secretion resume immediately after the last day of pill intake, which accounts for the risk of accidental pregnancy because of missed pills and for the rapid return of fertility on discontinuation of combined oral contraceptive use.
the development of new follicles starts during the 7-day pill-free interval.
other contraceptive actions:
cervical mucus changes:
endometrial changes:
actions as a "morning-after pill":
-
regimen consists of 2 doses of combined OCP, each containing at least 100 µg of ethinyl estradiol and 0.5 mg of levonorgestrel, administered 12 hours apart, initiated within 72 hours of intercourse (most effective if within 24hrs)
tendency to cause vomiting & thus in pill pack, provide anti-emetics such as metoclopramide & extra OCP's
will not prevent pregnancy once implantation has occurred
mechanism may involve a variety of actions depending on phase of menstrual cycle & includes:
inhibition of ovulation (only is some women) - as for OCP
suppressed or delayed LH surge
shortened “dysfunctional” luteal phase
endometrial changes - prevention of normal secretory endometrium
inhibition of fertilisation
inhibition of implantation
other effects of combined OCP's:
oestrogenic:
lowers androgen profiles improving hirsutism & acne:
increases sex hormone binding globulin
decreases LH secretion & thus reduces ovarian androgen production
decreases adrenal androgen production
decrease conversion of testosterone to the biologically active 5 alpha-androstane-diol
improves endothelial-dependent vasodilation
some may raise HDL
thrombogenic
as tend to worsen insulin resistance, obesity is a relative C/I
progestin:
some may decrease sex hormone binding globulin & potentially nullify the oestrogen component's anti-androgenic effects, however, it appears all current low dose OCP's result in lowering of free testosterone levels, although some pts may have transient increase in acne on commencement of OCP perhaps due to transient release of testosterone from sex hormone binding globulin.
3rd generation have increased thrombogenic effects
reduces risk of endometrial hyperplasia & possibly produces regular uterine withdrawal bleeding, thus helps reduce risk of uterine Ca
anti-atherogenic thus decrease risk of IHD
helps reduce risk of ovarian Ca
other combined effects
missed pill (combined oral contraceptive):
inactive tablet(s):
if 1 or more tablets are missed from the inactive tablets, no additional contraceptive precautions are necessary, thus continue taking as usual, ignoring missed tablets
if all missed, and then the next pack is not started on time, start as soon as remembered, additional contraception must be used for next 7 days.
active tablet(s):
delay < 12hrs then take
ASAP & continue as usual
delay > 12hrs then risk of contraceptive failure esp. if missed tablet is during 1st week or at end of pack
take missed tablet
ASAP, even if this means taking 2 at a time, but any earlier missed tablets are left in the pack
continue taking remainder of pack as usual
use additional contraceptive methods for next 7 days, if these extend into inactive section then skip the inactive section & start new pack in the active area on the next day instead
medications which can reduce the effectiveness of the OCP