Depot Formulation of MPA

Medroxyprogesterone acetate
Is a 17-acetoxy-6methylprogestin that has
progestogenic activity in
the human
Not metabolized as
rapidly as the parent
compound progesterone
so it can be given in
smaller amounts than
progesterone, with an
equivalent amount of
progestational activity.

Depot medroxyprogesterone acetate DMPA

Long-acting injectable
formulation of MPA, consists of
a crystalline suspension of this
progestational hormone.
The original contraceptive
dosage with the intramuscular
formulation (IM-DMPA) is
150mg.
Given by injection deep into
the gluteal or deltoid muscle,
after which the progestin is
released slowly into the
systemic circulation

 The area should not be

massaged, so that the drug
is released slowly into the
circulation and maintains its
contraceptive effectiveness
for at least 4 months.

The newer subcutaneous

formulation contains 104
mg of DMPA in 0.65 mL of
diluent and is injected into
the subcutaneous tissue of
the anterior thigh or
abdominal wall

 Subcutaneous
DMPA, though
delivers a lower
total dose of MPA
than IM-DMPA, has
a similar very high
level of
contraceptive
effectiveness

MULTIPLE MECHANISMS OF ACTION

therefore one of the most effective reversible
methods of contraception currently available
Three mechanisms of action are
involved.
First (the major effect): is
inhibition of ovulation.
Second: keeps the cervical
mucus thick and viscous, so
sperm are unlikely to reach
the oviduct and fertilize an
egg.
Third: the endometrium
becomes thin and does not
secrete sufficient glycogen to
provide nutrition for a
blastocyst entering the
endometrial cavity

Pharmacokinetics
MPA can be detected in the systemic
circulation within 30 minutes after its
IM injection.
Although serum MPA levels vary
among individuals, they rise steadily
to contraceptively effective
bloodlevels (>0.2ng/mL) within 24
hours after both IM and SC injection

 The pattern of IM-MPA clearance from

the circulation varies among different
studies according to the type of
assay used.

 After IM-DMPA was

administered to three
subjects, Ortiz and coworkers
assayed blood MPA levels Daily for 2 weeks, then
3x a week for the next 3 months,
and then
Weekly until MPA was
undetectable.

In two subjects, MPA levels

initially plateaued at 1.0 to
1.5 ng/mL for about
3months, after which they
declined slowly to about 0.2
ng/mL during the fifth month

 In a third subject,
the blood levels
were higher during
the first month,
then ranged
between 1.0 and
1.5 ng/mL for the
next 2 months, after
which there was a
further decline.

 MPA levels remained detectable in the circulation,

above 0.2ng/mL, for 7 to 9 months in all three
subjects, after which it was not detectable.
Estradiol (E2) levels were found to be in the
early to mid follicular phase range, but
consistently below 100 pg/mL during the first 4
months after injection.
After 4 to 6 months, when MPA levels decreased
to less than 0.5ng/ml

 Estradiol (E2) concentrations rose

preovulatory levels, indicating
follicular activity, but ovulation did not
occur, as evidenced by persistently
low progesterone levels.
Return of follicular activity preceded
the return of luteal activity by 2 to 3
months.

 This delay in resumption of luteal activity is

probably due to the fact that the circulating MPA
levels inhibit the positive feedback effect of the
rise of estradiol (E2) on the hypothalamic-pituitary
axis, which in the absence of MPA would stimulate
the midcycle release of LH.
The return of luteal activity in this study, indicated
by a rise in serum progesterone levels, did not
occur until 7 to 9 months after the injection, when
the MPA levels were less than 0.1ng/mL.

 Following injections of SubcutaneousDMPA, absorption of MPA is rapid and

rises above 0.2ng/mL (the contraceptive
effective level) within 24 hours.
Serum MPA levels peak about 8 days
after the injection and gradually decline
thereafter, but mean levels remain
above the contraceptively effective level
of 0.2 ng/mL for about 4 months

 Following injections of both IM-DMPA and SC-DMPA, serum

levels of FSH, E2, and progesterone are similar.
FSH levels remain in the mid follicular range for 3 months
without the midcycle FSH peak.
E2 levels remain suppressed and are similar to the levels on
days 1 to 3 of a pretreatment control cycle (40 to 60 pg/mL).
Progesterone levels are completely suppressed with both
types of formulations.
Thus, although low levels of ovarian follicular activity do
occur after IM-DMPA and SC-DMPA, ovulation is completely
suppressed.

 To obtain suppression of
ovulation in the initial injection
cycle, DMPA has to be
administered within several days
after the onset of menses.

 The product labeling states that

to ensure the woman is not
pregnant at the time of the first
injection, it must be given during
the first 5 days of the cycle.

 Use of contraceptive doses of

DMPA does not decrease
endogenous E2 levels to the
postmenopausal range and does
not cause symptoms of estrogen
deficiency