CONTRACEPTION
PITUITARY
RESPONSE ON
L. S. Wan,
M.D.,
G.
Department New
TO
LHRH
ORAL
York New
STIMULATION
IN
WOMEN
CONTRACEPTIVES
Weiss,
M.D.,
and M.
of Obstetrics University York,
Ph.D.
and Gynecology
School
New
Ganguly,
of Medicine
York
10016
ABSTRACT Gonadotropic
response
to an LHRH
two different
contraceptive
therapy,
months,
three
2-3
consecutive
had not token
ony oral
obtained
Ovulation response were
prior
in control in treated
no differences
not significantly greater taking were
mestranol found
half
Six women
during
to bolus injection subjects
the
long-
in the treated ethinyl
(Norinyl to LHRH
JANUARY
cycle
lower
contraceptives
l/50).
intervals
far over and who
as controls.
for two hours.
serum progesterone.
LH
that
There
of the controls.
groups.
FSH response than
was
in the patients
significant
contraceptive
19, 1977
was
of LH response
(Ovral)
No statistically
in the two oral
taking
Serum samples
The suppression
preparation
history
served
20-25.
than
and short-term
September
1978 VOL. 17 NO. I
day
who were
on a short-term
menstrual
by elevated
groups.
estradiol
preparation
for publication
oral
and at 20-minute
was confirmed
in FSH response
Accepted
taking
was significantly
between taking
were
were
for ot least one year,
intravenously
patients
on 12 patients
of the subjects
who had a normal
contraceptives
altered
in patients
Half
and the other
years.
150 ug LHRH was given were
bolus was tested
agents.
groups.
differences
CONTRACEPTION
INTRODUCTION Combination
oral
gonadotropic
secretion.
ponent
contraceptive
so follicular steroids
to determine bolus
whether
different
by the progestogen
(2).
oral
to their
contraceptives
alter
hormone
of chronicity
patients
The
I - Control
none had taken Group oral
patients
in this
Group:
oral
All
Contraceptives for 2-3
50 mcg + Norethindrone
Group
III
- Oral
performed
tests were
apart.
estrogen
with
two
into
Hospital
three
Center,
groups of six
day 20-25.
regular
menstrual
history
and
one year. These
women were
taking
contraceptives
and Ethinyl
two different
used were
Estradiol
Mestranol
50 mcg + Nor-
protein
with
method kits
control saline
20 minutes
measured
by radioimmunoassay
binding
by radioimmunoassay
Two
every
were
group of women
II for over three
in 3 ml normal
collected
and progesterone
This
(long-term):
as Group
in the morning.
were
was measured
competitive
cycle
The two oral l/50)
Bellevue
divided
had a normal
(short-term):
150 ug LHRH
serum samples
estrogen
responsiveness
Clinic,
were
for at least
months.
Contraceptives
All
Total
to a
We also have
mg (Ovral).
contraceptives
after,
responsiveness
METHODS
They
1 mg (Norinyl
the same oral
10 minutes
of the contra-
study was undertaken
hormone). on this
com-
preovulatory
actions
This
gonadotropic
out during
women
contraceptives
II - Oral
0.05
Additional
Planning
study.
study was carried
contraceptives
gestrel
AND
from the Family
to be subjects
each.
Group
on
contraceptives.
female
volunteered
The midcycle
releasing
of treatment
effects
by the estrogenic
effectiveness.
MATERIALS Eighteen
to have multiple
are inhibited (1).
(luteinizing
the effect oral
are felt
and FSH is inhibited
may contribute
dose of LHRH
determined
LH
development
LH surge may be blocked ceptive
agents
Basal
(4).
LH
provided
years.
serum samples
were
was given
Progesterone
and FSH
by NIAMDD
obtained
as a bolus.
There-
for two hours.
in each control
(3).
had been using
consecutive
were
sample.
Total
was measured
measured
in all
by the samples
(5,6).
RESULTS Control
Group:
In this
one concentration. illustrated LH release gradually
2
in Figures
of LH
was confirmed and FSH
by elevated
responses
to LHRH
serum progesterstimulation
is
1 and 2.
was noted returning
group ovulation
Composite
in all patients
to base1 ine,
after
less than
LHRH,
peaking
100 ng/ml
after
at 20 minutes
and then
80 minutes.
JANUARY
1978 VOL. 17 NO. 1
CONTRACEPTION
FSH response
to LHRH
was gradual,
and remained
slightly
above
Short-Term normal than
O.C.
ranges.
that
Group:
The control
LH release
was noted
of the control
the controls Long-Term
(Figure O.C.
The amplitude
Group:
Using
was lower
a paired
Since
Student’s than
l/50
After
LHRH
Five
(Figure
LH response FSH response group,
to that group
to that
1).
two groups (Figure
treated
within
of
normal
of the short-term
(Figure
subjects
in the response
we further
patients
curve
analyzed
group.
FSH response
2).
had significantly
after
the data
were
toking
and two to the peaked
was slightly
Norinyl
treatment
according
lower
in neither to different
than
that
(Figure than
response,
Three
patients
be-
group.
at 20 minutes, lower
significant
in individual
l/50.
long-term
to be more accentuated
variation
gradually
returning
of the control
to
group,
3).
the control
group.
this difference
However,
is not statistically
4).
There
group
the total
LH response
appeared
Group:
within was lower
was’similar
of LH and FSH were
similar
of the control
was not statistically
due to the great
Ovral
were
Its amolitude
(P40.02).
group
stimulation,
but the difference
short-term
observed
fell
agents.
The response
significant
levels
any difference
groups,
Group:
FSH response
of LHRH.
six oatients.
from the other
t test,
to the short-term
baseline.
that
the controls
Oral contraceptive Norinyl
The level
administration
The F’SH response
1).
at 20 minutes,
different
nor long-term
Longed
(Figure
than
we did not observe
short-
at 60 minutes.
LH and FSH levels in all
The baseline
peaked
was not significantly
LH elevation
group
a peak
at 2 hours after
2).
LH release
ranges.
reaching
50 ng/ml
were
seven
patients
and four
in the
long-term
was significantly appeared
the difference
suppressed
to be slightly
in this group.
as compared
suppressed.
is not statistically
Three
patients
were
in the
group. to the controls
However,
significant
(Figure
compared
(Figure to the
3). control
4).
DISCUSSION The gonadotropic menstrual that
all
cycle patients
exogenously
JANUARY
response (7,8,9).
to LHRH
varies
We selected
had circulating
the
during
the different
luteal
progestational
phases of the
phase to carry
steroids,
either
out this study so endogenously
or
administered.
1978 VOL. 17 NO. 1
3
CONTRACEPTION
I
I
I
I
I
-10 0
20
40
60
80
I
TIME
Figure
1.
LH Response to LHRH
IN
Challenge
I
I
100
120
MINUTES
in Control,
Short-Term
and Long-Term
Groups
LHRH
I -?O 0
&-A
Short
Term OC
i6l
A---A
Long
Jeerm OC
/6/
1
I
I
I
I
I
20
40
60
80
100
120
TIME
Figure
2.
FSH Response to LHRH
Challenge
IN
MINUTES
in Control,
Short-Term
and Long-Term
Groups
4
JANUARY 1978 VOL. 17 NO. 1
CONTRACEPTION
250
f
200
\ y
150
=
100 I 50 1 I
-10
0
I
I
I
I
20
40
60
80
TIME
Figure 3.
IN
LH Response to LHRH Challenge
I
100
I
120
MINUTES
in Control,
Norinyl
11.50 and Ovral
Groups
I
I
I
I
I
I
-10 0
20
40
60
80
I
TIME
Figure 4.
FSH Response to LHRH Challenge
IN
I
I _
100
120
Norinyl
l/50
MINUTES
in Control,
and Ovral
Groups
JANUARY
1978 VOL. 17 NO. 1
5
CONTRACEPTION
Our
findings
Oral taking This
are similar
contraceptives ethinyl
estradiol
alteration
subjects
in LH
taking
oral
of oral
stimulus LHRH
response
preperation,
response
(10) and Mishel bolus.
the LH response
wos significantly
is not due to the presence since
cannot
differentiate
contraceptives.
of synthesis
of LH
the controls
suppressed.
of progestogen
were
in their
in the
luteol
phase
a pituitary
A hypothalamic SO there
from a hypothalamic site
of action
may be less releasable
might
site
of
decrease
LH in reponse
the
to an
bolus.
By the criteria
of this
responsiveness.
This
amenorrheo reason
study,
chronicity
is consistent
does not correlate
for periodically
recovery,
since
with
with
of therapy
does not olter
the clinical
observations
the length
discontinuing
pituitary
term contraceptive
oral
responsiveness
of theropy.
contraceptives is similar
to allow
in potients
produced of different
agents
mestranol
for pituitary ond short-
regimen.
et al. (10) suggests thot pituitary block -Our findings is a dose reloted phenomenon.
suppressive
postpill
seems to be no
on long-
Dericks-Tan
two different
gonadotropic that
There
steroids than
I -et al .( 11). In the group
et al. t;anLHRH
progesterone.
type of study
action
FSH
contraceptives
and hod circulating This
to those of Dericks-Tan
did not alter
(in
suggest:
Norinyl
action
(a) ethinyl
(in
and (b) norgestrel
l/50);
of ethinyl
estradiol
by oral
Ovral)
LH
contraceptive response
is a stronger
(in Ovrol)
with
suppressant
moy potentiate
the
estrodiol. CONCLUSIONS
1.
LH response somewhat
2.
There
is no difference
ceptive 3.
The
appears
while
FSH
between
in potients
response
on oral
contraceptives
is not significantly
the long-term
and short-term
is
altered. oral
contro-
groups.
average
different
6
to o bolus dose of LHRH
suppressed,
oral
response
to LHRH
contraceptive
to be a more potent
stimulotion
agents.
differs
An equal
suppressant
in patients dose of ethinyl
who are taking estradiol
than mestranol.
JANUARY
1978 VOL. 17 NO. 1
CONTRACEPTION
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7