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Female Hormonal Contraception

What are the attributes of the ideal contraceptive?
Reliable, safe, reversible, cost-effective, easy to use, no discomfort, minimised side effects and readily
available.
Contraception Methods
Combined oral contraception pill (COCP)
COCP is an oral contraceptive that contains a synthetic oestrogen such as ethinyl oestradiol and a
synthetic progesterone such as progestagen e.g. for example, Microgynon: 30 micrograms of ethinyl
estradiol, 0.15mg levonorgestrel. They are currently used by more than 100 million women
worldwide.
How does it work?
The basis of this treatment is maintaining high levels of gonadal steroids (high levels of oestrogen and
progestagen) so altering the gonadotrophin release and the state of the reproductive tract, making it
unsuitable for a successful pregnancy.
What are the effects of constant high levels of oestrogen and progestagen?
The constant high level of oestrogen and progestagen together
Inhibits ovulation
Oestrogen and progestagen combination inhibits tertiary ovarian follicle growth and prevents
the surge of FSH and LH secretion from the pituitary that normally causes ovulation in the
mid-cycle LH surge.
This pill mimics the negative feedback effects of oestrogen and progestagen present during
the luteal phase of the menstrual cycle and pregnancy.
On the ovary - decreased sensitivity towards gonadotrophins and so steroidogenesis is
abnormal.
On the fallopian tubes - the motility, secretion and metabolism is abnormal.
On the uterus - motility and secretion are abnormal and the endometrium is unreceptive to
the embryo because of the oestrogen: progestagen ratio, so do not support implantation.
On the cervix - under the influence of high levels of progestagen the cervical mucus is thick
and unsuitable for sperm migration.
On the sperm - sperm capacitation may be inhibited, probably due to high levels of
progestagens.


Definitions
Contraception: the deliberate use of artificial methods or other techniques to prevent pregnancy as a
consequence of sexual intercourse
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Which kinds of progestagens are used?
The progestagens are mainly testosterone derivatives so androgenic effects such as acne/spots may
result while taking the pill.
Types of progestagens used:
Estranes............norethindrone (POP)
Gananes...........levonorgestrel, norgestrel, desogestrel, norgestrimate
Drosperinone......derivative of spironalactone
Cyproterone acetate......antiandrogen
Decreased androgenesity.
How is COCP used?
The pills come in 21 or 28-day cycle packages.
A woman will take one hormone-containing pill each day, usually beginning on the Sunday
after her last menses began.
Then she continues for 21 days. During this time, ovulation is suppressed. She then either
stops taking any pills for 7 days. After stopping the hormonal-pill, menstruation begins.
A woman is unlikely to get pregnant during the 7-day period when she is not taking the
hormonal-pill because she is menstruating for a few days and an embryo would not implant.
Furthermore, 7 days is not enough for follicular growth and ovulation to occur.
If she misses 1 day of taking the pill, then she can take two the next day with no loss of
protection. If however, she misses 2 or more days, she should stop taking the pill for 7 days
and then begin a new pill cycle; other contraceptive methods should be used such as condom,
diaphragm during this 7 day period as pregnancy is certainly possible.
There are three kinds of COCP
Monophasic: the pill has the same dose of oestrogen and progestagen and could be taken for
28 days with a placebo or 21 days with a break.
Biphasic (and triphasic): these pills are designed to more accurately mimic the changing
hormonal levels in a natural cycle. Each package contains two 14-days or three 7-day
sequence of pills with changing amount of oestrogen and/or progestagen. In biphasic COCP,
there is lower progestagens in the 1
st
part of the pills to reduce side effects.
Triphasic: changes every 7 days (may have changing oestrogen and progestagens) and is
usually given if progesterone-related side effects are present.



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Examples of these pills:
Monophasic: Alesse and Brevicon
Biphasic combination birth control pills have pills with two different levels of hormones; for
example, hormone levels may be higher the first 10 days, then lower the next 11 days. Ortho-
Novum 10/11, Necon 10/11, Mircette and Jenest-28
Triphasic combination birth control pills, like Ortho-Novum 7/7/7, Ortho Tri-Cyclen, Tri-
Levien, Tri-Norinyl and Triphasil, have pills with three different levels of hormones.
New pills
Seasonique
Same steroids but women experiences only 4 periods a year. It also contains placebo pills but
is continuous
Disadvantages: very thick endometrium, which may result in some bleeding.
Skipping the break ok with any monophasic pill...others may give break-through bleeding
Flexyness
3mg DRSP and 20ug EE
New Clyk dispenser with alarm
flexible extended-use (24 to 120 days per cycle)
women given flexibility = 41 days bleeding/yr
COCP =66 days
Fixed extended regimen =60 days
Side effects of COCP
Mild side effects: some women may experience these.
Oestrogen related: nausea, bloating, fluid retention, slight weight gain, mood changes,
headaches etc.
Serious side effects:
May be a small increased risk that COCP may cause breast and cervical cancer
Can pose a risk to women who are predisposed to CVD (e.g. hypertension)
Some evidence suggests that COCP use can increase the levels of triglycerides and
cholesterol in the blood
Beneficial side effects:
Effective contraception (1 in 100 pregnancy rate)
Decreases risk of ovarian and endometrial cancer
Alleviates acne, excess body hair, breasts cysts, irregular menstrual periods and symptoms of
premenstrual syndrome
Also a reduction in menstrual loss, and therefore protects women against anaemia
Suppression of uterine fibroids



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Non-oral hormonal contraception
Patch/Transdermal
Oestrogens and progestagens can be delivered across the skin through the contraceptive patch
e.g. EVRA
The thin patch is worn on the skin where it provides a constant flow of hormones into the
bloodstream
Should be changed once a week for 3 weeks. It is important to apply the patch on the same
day for the 3 consecutive weeks. The forth week is patch free and menstruation occurs at this
time.
As effective as the COCP and also prevents ovulation and thickening of the cervical mucus
inhibits sperm movements.
Advantages: ease of use, no daily pills, can apply herself and its absorbed by the stomach,
so effective even if with vomiting or diarrhoea. Also reduces pill-associated nausea
Disadvantages: similar to COCP
About 10 per month
Intra-uterine contraceptive devices (IUCD)
T-shaped piece of flexible plastic placed within the lumen of the uterus through the cervix.
The primary effects occurs prior to fertilisation as the presence of the IUCD reduces sperm
motility and viability, resulting in reduced sperm counts in the uterus and cervix.
Also affects the development and maturation of the ovum and prevents implantation of the
blastocyst.
Causes an inflammatory reaction (foreign body) and thus increasing the number of white
blood cells in the uterus. It is thought that the breakdown products of white blood cells are
toxic to the blastocysts, ovum and the sperm.
Replaced around 5-10 years depending on the type
Types:
Copper-bearing IUCD: GyneFix IUI 5yr
Copper bearing intrauterine contraceptive devices are inserted into the uterus by suitably
trained practitioners and may be left in situ long term
It works by producing a hostile environment for implantation and is toxic to both the egg and
sperm
Non-copper bearing: Mirena IUS, which contains progesterone.
How does it work?
Locally releases a progestagen called Levonorgestrel daily into the uterine cavity
The progestagen prevents implantation and thickens the cervical mucus thus inhibiting sperm
transport through it.
Suitable for older women who have completed her family
Can be left in for 5 years
Advantages: long-term use, useful for older women, protects the endometrium from
hyperplasia due to oestrogen treatment


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Disadvantages of using IUCD
Pain as may be uncomfortable and excessive bleeding
Increased possibility of tubal infections for women in unstable relationships with numerous
sexual partners: infections include Chlamydia and Gonorrhoea
Prolonged menses and inter-menstrual bleeding
May stimulate prostaglandin release and therefore stimulate uterine contraction and loss of
the endometrium
High rate of infection when inserting the device (2-3 weeks after insertion) and can be treated
with antibiotics
Perforation of the uterus
If pregnancy occurs while there is an IUCD in place, there is a significant increase in risk of
abortion (50% in the first three months) also increases risk of ectopic pregnancies
Injectable Hormones
Injectable progestagen such as Implanon
Contains 68mg of etonogestrel
Lasts for three years
The progestagen is continuously released into the circulation and it works by thickening the
cervical mucus thus preventing penetration and supressing ovulation.
Advantages: effective birth control for 3 years, safe to use while breast-feeding, can be taken
by women who cant take oestrogen, less menstrual bleeding and rapid return to fertility
following removal
Disadvantages: unpredictable and irregular menstrual bleeding, must be inserted by a trained
health professional, does not protect against STDs and may cause headaches.
As of October 2010, Implanon was discontinued and replaced by Nexplanon, a newer version
of the implant designed to reduce the risk of insertion errors.
Nexplanon implants also contain barium, which allows them to be easily located using X-rays
and CT scans.
I nsertion and removal: slides
Intramuscularly hormones injection (depot)
Lasts 3 months
Intramuscular: arm or buttock
150mg medroxyprogesterone acetate (provera)
Progesterone: works by blocking the LH surge, thus blocking ovulation.
New subQ version has less provera
Disadvantages: cant take it out after administration as it is inserted deep into the muscle,
irregular bleeding, pain on insertion and increases risk of ectopic pregnancy
Advantages: good for endometriosis
Vaginal ring
Ring releases progesterone and oestrogen
Trade name NuvaRing.
In vagina for three weeks out of every four, then disposed of. Bleed during ring-free
week. After a week's break, insert new ring in.

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Emergency contraception
This involves administration of oestrogens and/or progestagens straight after having
unprotected sex.
Two types: Post-coital pill and the copper bearing IUCDs
Post-coital Pill
A high dose of oestrogen given within 72 hours after unprotected sexual intercourse (UPSI)
followed 12 hours later by a second dose, will prevent implantation of the fertilised egg in 3
out of 4 potential pregnancies.
The oestrogen either prevents the passage of the egg through the oviduct by causing a spasm
of the smooth muscle wall (tube-lock) or by inducing contractions of the smooth muscle
which speeds the passage of the egg so that it reaches the uterine lumen before the
endometrium is prepared for implantation.
Levonorgestrel, Levonelle 2 works by postponing or abolishing ovulation and prevents 7
out of 8 pregnancies
This treatment can inhibit ovulation, interfere with the pre-embryo down the oviduct or alter
the endometrium so implantation does not occur.
Emergency contraceptive pills are not effective if implantation has already occurred.
Copper bearing IUCDs
Up to 5 days after presumed ovulation or 5 days after one single episode of UPSI at any time
of the cycle
Failure extremely rare
Levonelle
o Levonelle 2 used to be 2 tablets each containing 750 micrograms of Levonorgestrel
o Now single tablet of 1500 micrograms taken as soon as possible after UPSI, but always within
72 hours.
o Very little nausea
o Only contraindicated in women taking very potent liver enzyme medication (anti TB)
o WHO has also shown that the efficacy is still good at 5 days 120hrs) after UPSI (unlicensed
use)
o Addition of prog and removal of effects of prog?
o Inhibition of ovulation if taken before ovulation
o Interference with endometrium also







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Essay questions:
o How does our understanding of the menstrual cycle permit the use of hormonal
contraceptives?
o What are the desirable features of the perfect female hormonal contraceptive? Describe how 3
different types of products currently on the market aim to achieve these ends
o What are the features of a perfect contraception? Describe one method and how it meets its
requirements.