4. TYPES
THE
THE COMBINED
PROGESTOGEN-
PILL
ONLY PILL
5. The combined pill
(combinations of an oestrogen with a
progestogen)
Formulations may be :
1. Monophasic (each tablet contains a fixed
amount of estrogen and progestin);
2. Biphasic (each tablet contains a fixed
amount of estrogen, while the amount of
progestin increases in the second half of
the cycle); or
3. Triphasic (the amount of estrogen may be
fixed or variable, while the amount of
progestin increases in 3 equal phases).
6. The combined pill
(combinations of an oestrogen with a
progestogen)
The oestrogen in most combined preparations
(second-generation pills) is ethinylestradiol,
although a few preparations contain mestranol
instead.
The progestogen may be norethisterone,
levonorgestrel, ethynodiol, or-in 'third-
generation' pills-desogestrel or gestodene,
which are more potent, have less androgenic
action and cause less change in lipoprotein
metabolism, but which probably cause a greater
risk of thromboembolism than do second-
generation preparations.
7. The combined pill
The oestrogen content is generally 20-50μg of
ethinylestradiol or its equivalent, and a
preparation is chosen with the lowest oestrogen
and progestogen content that is well tolerated
and gives good cycle control in the individual
woman.
This combined pill is taken for 21 consecutive
days followed by 7 pill-free days, which causes
a withdrawal bleed. Normal cycles of
menstruation usually commence fairly soon after
discontinuing treatment.
8. mode of action
oestrogen inhibits secretion of FSH via negative
feedback on the anterior pituitary, and thus
suppresses development of the ovarian follicle
progestogen inhibits secretion of LH and thus
prevents ovulation; it also makes the cervical
mucus less suitable for the passage of sperm
oestrogen and progestogen act in concert to alter
the endometrium in such a way as to discourage
implantation.
They may also interfere with the coordinated
contractions of cervix, uterus and fallopian tubes
that facilitate fertilisation and implantation.
10. Common adverse effects
weight gain, owing to fluid retention or an
anabolic effect, or both
mild nausea, flushing, dizziness, depression
or irritability
skin changes (e.g. acne and/or an increase in
pigmentation)
amenorrhoea of variable duration on
cessation of taking the pill.
11. POTENTIAL ADVERSE
EFFECTS
Cardiovascular: Although rare, the most serious
adverse effect of oral contraceptives is cardiovascular
disease, including thromboembolism, thrombophlebitis,
hypertension, increased incidence of myocardial
infarction, and cerebral and coronary thrombosis. These
adverse effects are most common among women who
smoke and who are older than 35 years, although they
may affect women of any age.
Carcinogenicity: Oral contraceptives have been shown
to decrease the incidence of endometrial and ovarian
cancer. Their ability to induce other neoplasms is
controversial. The production of benign tumors of the
liver that may rupture and hemorrhage is rare.
12. POTENTIAL ADVERSE
EFFECTS
Metabolic: Abnormal glucose tolerance (similar to the
changes seen in pregnancy) is sometimes associated
with oral contraceptives. Weight gain is common in
women who are taking the nortestosterone derivatives.
Serum lipids: The combination pill causes a change in
the serum lipoprotein profile: Estrogen causes an
increase in HDL and a decrease in LDL (a desirable
occurrence), whereas progestins may negate some of the
beneficial effects of estrogen. [Note: The potent progestin
norgestrel causes the greatest increase in the LDL:HDL
ratio. Therefore, estrogen-dominant preparations are best
for individuals with elevated serum cholesterol.]
13. Beneficial effects
The combined pill markedly decreases
menstrual symptoms such as irregular
periods and intermenstrual bleeding.
Iron deficiency anaemia and premenstrual
tension are reduced, as are benign breast
disease, uterine fibroids and functional cysts
of the ovaries.
14. The progestogen-only pill
The drugs used in progestogen-
only pills include
norethisterone, levonorgestrel or
ethynodiol.
The pill is taken daily without
interruption.
15. mode of action
The mode of action is primarily on the
cervical mucus, which is made
inhospitable to sperm. The
progestogen probably also hinders
implantation through its effect on the
endometrium and on the motility and
secretions of the fallopian tubes
16. Potential beneficial and
unwanted effects
Progestogen-only contraceptives offer a
suitable alternative to the combined pill for
some women in whom oestrogen is
contraindicated, and are suitable for women
whose blood pressure increases
unacceptably during treatment with
oestrogen.
However, their contraceptive effect is less
reliable than that of the combination pill, and
missing a dose may result in conception.
Disturbances of menstruation (especially
irregular bleeding) are common.
17. Pharmacokinetics of oral
contraceptives
Combined and progestogen-only oral
contraceptives are metabolised by hepatic
cytochrome P450 enzymes.
Because the minimum effective dose of oestrogen
is used (in order to avoid excess risk of
thromboembolism), any increase in its clearance
may result in contraceptive failure, and indeed
enzyme-inducing drugs can have this effect not
only for combined but also for progesterone-only
pills.
Such drugs include rifampicin and rifabutin, as
well as carbamazepine, phenytoin, griseofulvin
and others.
18. Broad-spectrum antibiotics such as amoxicillin can
disturb Enterohepatic recycling by altering the
intestinal flora, and cause failure of the combined
pill. This does not occur with progesterone-only
pills.
19. Ormeloxifene
Ormeloxifene is a selective estrogen
receptor modulator (SERM).
Marketed as Centchroman, Centron, or
Saheli, it is pill that is taken once per week.
Ormeloxifene is legally available only
in India.
20. POSTCOITAL (EMERGENCY)
CONTRACEPTION
Oral administration of
levonorgestrel, alone (1.50 mg usually) or
combined with oestrogen, is effective if
taken within 72 hours of unprotected
intercourse, repeated 12 hours later.
Nausea and vomiting are common.
(replacement tablets can be taken with an
antiemetic such as domperidone).
A single dose of mifepristone has also been
used for emergency contraception.
21.
22. From Fertilization to Implantation
Figure 1 (click to enlarge)
To understand and evaluate chemical methods of birth control, it is helpful to have a basic
grasp of the mechanism and timing of the biological events that bring a new human life into the
world. (For more complete coverage of this topic see the DVD Fearfully and Wonderfully
Made.)
About every 28 days, a woman with a normal menstrual cycle will release an egg (occasionally
more than one) from her ovary (see Figure 1). This process, called “ovulation,” is under the
control of hormones produced in the pituitary and ovary. Once ejected from the ovary, the egg
enters a tube called the “oviduct” (or “fallopian tube”) which transports the egg to the uterus. If
fertilization occurs, it normally occurs in the first third of the oviduct and typically within 12 to 24
hours after ovulation.
Fertilization is completed when the genetic material of male germ cell (the sperm) combines
with genetic material of the female germ cell (the egg)—a momentous event called
“conception.” After fertilization, the fertilized egg (now called a “zygote”) continues on its
passage toward the uterus, where it will arrive about three days from the time of ovulation.
Along the way the zygote will divide a few times to produce a ball of cells called a “morula”
(see Figure 1).
Once in the uterus the morula continues to divide and by the fifth day becomes a hollow ball of
cells called a “blastocyst,” which contains the embryo (an outer layer of cells will form the
placenta). By about the sixth day, the blastocyst burrows into the wall of the uterus, a process
called “implantation,” and here it will continue to grow. During the first two months of
development after fertilization, the developing baby is called an “embryo” (later in development
called a “fetus”). Despite all the name changes, the whole process from fertilization to birth is a
continuous and marvelously complex development of a human baby.
23.
24. Major adverse effects: The major adverse effects are breast
fullness, depression, fluid retention, headache, nausea, and vomiting.
Cardiovascular: Although rare, the most serious adverse effect of oral
contraceptives is cardiovascular disease, including
thromboembolism, thrombophlebitis, hypertension, increased incidence of
myocardial infarction, and cerebral and coronary thrombosis. These adverse
effects are most common among women who smoke and who are older than 35
years, although they may affect women of any age.
Carcinogenicity: Oral contraceptives have been shown to decrease the incidence
of endometrial and ovarian cancer. Their ability to induce other neoplasms is
controversial. The production of benign tumors of the liver that may rupture and
hemorrhage is rare.
Metabolic: Abnormal glucose tolerance (similar to the changes seen in pregnancy)
is sometimes associated with oral contraceptives. Weight gain is common in
women who are taking the nortestosterone derivatives.
Serum lipids: The combination pill causes a change in the serum lipoprotein
profile: Estrogen causes an increase in HDL and a decrease in LDL (a desirable
occurrence), whereas progestins may negate some of the beneficial effects of
estrogen. [Note: The potent progestin norgestrel causes the greatest increase in
the LDL:HDL ratio. Therefore, estrogen-dominant preparations are best for
individuals with elevated serum cholesterol.]
Contraindications: Oral contraceptives are contraindicated in the presence of
cerebrovascular and thromboembolic disease, estrogen-dependent
neoplasms, liver disease, and pregnancy. Combination oral contraceptives should
not be used in patients over the age of 35 who are heavy smokers.
25.
26. The endometrium slowly gets built up before ovulation
(the proliferative phase) and then reaches its peak in
the secretory phase (shortly after ovulation{and
conception if it has occurred}). The endometrium is
"ready for the newly conceived child to implant" when it
reaches its peak in the secretory phase a few days after
ovulation. We note that the blood flow and thus the
oxygen and nutrients to the glandular cells of the
endometrium increases through the cycle as the spiral
arteries enlarge during the secretory phase. The size of
the endometrial glands also enlarge in the secretory
phase. The glands contain important nutritional building
blocks for the unborn child who is about to
implant, including glycogen (a type of
sugar), mucopolysaccharides (ie, they supply certain
building blocks for a cell's growth) and lipids (fats) 5.
