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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Menstrual

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7