Life table analysis of a clinical study of a once-a-month oral steroid contraceptive: Quinestrol — Quingestanol

LIFE TABLE ANALYSIS OF

A ONCE-A-MONTH

OF A CLINICAL ORAL

QUINESTROL

Daniel

STEROID

STUDY

CONTRACEPTIVE:

- QUINGESTANOL

R.

Mishell,

Jr.,

M.D.

and Norman

Section Department University

D.

Freid,

M.D.

of Reproductive of Obstetrics

of Southern

Biology

and

California

Los Angeles,

Gynecology

School

California

of Medicine

90033

ABSTRACT A clinical 2.0

study of a long-acting

mg quinestrol

31 -month

period.

and

2.5

A total

women-months

experience

at the end of

1 year

pregnancy, cumulative method

Accepted

JULY

11.2

mte

the event

VOL.

bleeding

were

May

and

8 NO. 1

containing

was undertaken

Life-table

1 year

during

a

in the study and 2,781 analysis

of event

for discontinuation

17.3

in this population

7,

formulation,

enrolled

mtes

at the end of

accepted

for publication

women

steroid acetate,

was accumulated.

for abnormal

was not well

1973

of 212

revealed

continuation

oml

mg quingestanol

for other was only

rates

to be 7.3

medical

reasons.

46.9,

indicating

for The this

group.

1973

37

CONTRACEPTION

INTRODUCTION Long-acting frequency initial

clinical

This oral acting

testing

are

quinestrol 1 -ether

is ingested

The and

bleeding

the progestogen

are

generally

both effective rates

in the

determining port,

is included

and acceptable published

studies,

ation

Life-table

rates

From October

,1969,

in the

a once-a-month

to June,

Family oral

lactating filled

cycle

were

these

in the study.

postpartum

women

postpartum at that

day of their

published

to determine methods

as

continuation

for accurately

not used.

In this re-

of contraception event

and

are

continu-

subjects, next

with

selection these 212 started

they

a history 60 days,

were

menses.

For all

in addition

elected

bleeding

as those who were

of 212

told

144 or 68% method

to ingest

to ingest

period

the first

their

were

to steroid who

ful-

and were

less than

of contraception.

who had resumed

subjects,

women

to use this method

women,

informed

to other

of intermenstrual

A total

of

were

The usual contraindications

women

instructed

a method

Hospital

as well

had a menstrual

were

Postpartum

requesting

of Women’s

using this

had not yet

visit,

time.

women

participation.

they

METHODS

was available

from the study.

Of

when

capsule

other

withdrawal

of contraception

to calculate

Clinic

of more than

for patient

6-week as all

Women

length

excluded

months postpartum

1970,

Planning

also excluded

the criteria

enrolled

to induce

rates were

AND

contraceptive

methods of contraception.

contraception

ace-

(7).

contraception

or menstrual

Quin-

in the subsequent

of contraception

as life-table

utilized

MATERIALS

that

ovulation

study using this method

methods were

fat.

capsule.

It is difficult

however,

in both animals

of norethindrone

this method

and pregnancy

the results of an additional

presented.

indicate

(l-6).

both continuation

of the

These mg of

from body

derivative

this method

and

release

2.0

a 3-cyclopentyl

activity

in the formulation

studies with favorable

acetate.

containing

to inhibit

(l-6).

consists of a long-

Quinestrol,

ether

ingestion

has undergone

South America

quingestanol

has prolonged

is utilized

a few days after

and

capsule

acetate.

enol

of decreased

formulation

4 weeks,

in and subsequent

estrogen

Reports of clinical to date

every

oil-filled

is a 3-cyclopentyl

within

oral

in Mexico

estradiol,

of storage

long-acting

the advantage

and a progestogen,

in a single

mg of quingestanol

man as a result

cycle

which

of ethynol

acetate

have

long-acting centers

quinestrol,

and 2.5

gestanol

One

in several

formulated

derivative

tate.

contraceptives

contraceptive,

estrogen,

steroids

and

steroid

of administration,

first

the second

.ITV,Y

3 If

at the time

of their

quinestrol-quingestanol menstruation, capsule

capsule

1973

as well

on the

first

was scheduled

VOT,.

8 NO.

1

CONTRACEPTION

to be taken

22 days after

after,

regardless

nancy

with

first

this

patients The

Prior

time a general kept records

patients

at which given.

were

time

foam, physical

By August

and pelvic

study

was discontinued. analyzed

with

as well

Four

life-table

months

later,

during

the first

were

month The

performed.

as incidental

planning

in the

by a physician complaints.

nurse practitioner,

and a new supply

information

of preg-

contraceptive

examined

examination

episode

tabulated

1972,sufficient

were

were

28 days there-

to be highest

to the steroids

3 months by a family

records were

every

the incidence

to use a local

the patients

of each bleeding

seen every

these

Since

has been reported

in addition

to treatment,

capsules

bleeding.

the women were advised

such as vaginal

of treatment. at which

and subsequent

of uterine

method of contraception

month of use (3),

method,

the first

of the time

of medication

had been accumulated data concerning

was

and the

pertinent

events

methods.

TABLE NET

CUMULATIVE

DISCONTINUATION

RATES

PER

100 WOMEN

Rates of Women Types

of Termination

Completing

d

Pregnancy Abnormal Other

Bleeding

Medical

Persona I

2.4

11.2

4.3

17.3

7.2

Moved

8.2

I

I

1.4

Investigators

Choice

12.0 4.8

0.0

0.5 I

I

I

Cumulative

Discontinuation

Cumulotive

Continuation

17.2

Rate Rate

82.8

I

33.1

I

I

66.9

I

I

53.1 46.9

RESULTS A total ception 212

of 2,781

women-months

had been accumulated

women enrolled

stated

they

.1l.I,Y

lo;:3

had taken

at the

in the study, the pills

VOL. 8 NO. 1

experience

time the study

with

19 became pregnant;

as directed.

this

method of contra-

was terminated.

Of

the

14 of these women

An additional

5 women

had de-

CONTRACEPTION

layed

taking

in which

the

months were patient

1.9,

local

months,

rates beyond

this time

mte

Only

Only longer

were

medical

medical

away.

year

periods,

while

the

first

reasons for stopping

this method

year.

1,828

Another

10

one-half

of abnormal

of

bleed-

in the first

complained

because

were

of

months.

Approximately

5 discontinued

discon-

A total

12 ordinal

majority

event using this

cumulative

who discontinued

the

problems,

one

for 31

continued

did so because

the 24 women

12

Only

calculate

100 women.

in the

moved

in the first Of

women

in the first

lost-to-follow-up

bleeding

menstrual

per

cycle 6 and

to use an addi-

continued

to reliably

12 months and

was 53.1

as they

reasons.

of abnormal

the study

1 year

of the

(Table).

but she failed

93 of the 212

than

1 year

who discontinued

heavier

The other

beyond

day

the end of 3,

respectively

though

was accumulated

8 women

because

and/or

continued

period.

rates at

cycle,

Even

for

the scheduled

100 women,

treatment

from follow-up

ing or other

per

method.

experience

released

the women

7.7

at the end of

women-months

and

patients

days after

The pregnancy

in the first

of contmception

tinuation

year

and

contraceptive

too few

method

for a few

occurred. 3.4

conceived

tional

were

capsule

conception

of longer

of amenorrhea.

mainly

headache,

chloasma

with

once-a-month

nausea.

DISCUSSION In contrast administration to have

to other

clinical

limited

usefulness

women

years,

years

100 women

reported

higher

in earlier

is similar

in this population

than

studies

to the

the

pregnancy

the 0.8

to 4.0

rate

it

of 7.7

per

was 8.2

pregnancies

The pregnancy

(1- 6).

rate

showed

method.

women-months,

appreciably

years

experience

acetate

as a contmceptive

In this study of 2,781 100 women

studies,

of quinestrol-quingestanol

100 women

rate

per

per 100

of 8.2

per

at the end of 1

year. Only

4 of the

so for planning reasons other after

the

method

than

Only

when

noted

to be the

which

time

tance

of taking

trolled

field

the

one

who discontinued

the 35 patients All

pregnancy

incidence

of accidental

These patients

were

given

new medication

the capsules

as directed.

in this study would

for personal 6

19 pregnancies

pregnancy

has been

seen every

and

reinstructed

Therefore, than

it would that

months

were

in the

were

be lower

reasons did

within

in this study occurred

(3).

mte

pregnant

but 5 of the

highest

they

for personal

who discontinued

8 became

pregnancy,

was ingested.

failure.

the pregnancy

Of

planning

last pill

ment cycle,

39 patients

pregnancy.

three

first

due

to

treat-

previously months,

as to the

at

impor-

be expected

of less carefully

that con-

trials.

.llXY

1973

VOL. 8 NO. I

CONTRACEPTION

The acceptability group was not good, for

more than one

method

that

medical

more,

Although reports of contmception was well

of these

followed

It has been

noted

bleeding

method

of contmception

as well

bleeding

of patients bleeding

reports

reports,

for more than

drawal abnormal

began

in this population

continued

one year

that

there

is an

might

increased

bleeding

in the postpartum

in only

period,

have

been

in the postpartum a minority

enrolled

rates.

Further-

in the study who

was less than 50%.

as breakthrough

treatment

this bleed-

studies indilife-table

of continuation

of subjects

incidence

in women

of heavy

who begin

period.

with-

this

This discontinuation elevated because the

mte for majority

Nevertheless, abnormal discontinuing this method

of the patients

of contraception.

Only 21% of those women discontinuing of abnormal bleeding and 5 of these 24 women

so because

using this method

of other clinical accepted (l-6),

for analysis

the number

in this study

occurred

of contraception

of the women

More than one third of the subjects discontinued for pertinent events such as pregnancy, abnormal

not used in these

in each

half

reasons.

this method

methods were were

year.

of contraception

ing or other cate

of this method

as less than

in the first discontinued

year for

did

amenorrhea.

The unfavorable differ

possible

that

account

for the

mulative per

contrast

continuation

ceptives

are

‘fork

at

Planned

published

of this unique accumtely

nearly

type

determine

in this study It is

trials.

studied might partially However, the cu-

and

and

Feldman

Center trials

and

with

this method

more completely compare life-table

1

shown that

users,

82.0

oml

steroid

continuation

of contraception

the effectiveness contraceptive.

cumula-

and

81.9

will

as other

be used for anolysis trials.

soon be

and acceptance In order to

rates of this as well

methods should

of the results of clinical

VOL. 8 NO.

have

IUD

at the end of one year in the Buffalo-New It is hoped that the results of other re(8).

of long-acting

to publication

JXTLY 1973

groups being

contmceptive

identical

determine

methods of contraception, prior

rates

clinical

of this study to others.

as Lippes

for oml

clinical

to help

continuation

of earlier

for multiparous IUD users in the same clinic is 80 Continuation rates for other oml contra1 year.

similar,

Parenthood

completed

in population

in results

mte

mtes

are

rates and reports

the end of

probably

continuation

respectively, cently

favorable

the difference

100 women

ttve

data

pregnancy

from the genemlly

of the

CONTRACEPTION

REFERENCES 1.

Rubio, with

B.,

Fertil.

2.

Steril.

Larmnga, oral

Mischler,

T.W.

a once-a-month 23:734,

A.

and

and

Berman,

Further

experience

1972.

Berman,

contraceptive:

E.:

Quinestrol-Quingestanol.

contraceptive:

Clinical

E.:

study of a once-a-month Contraception

Quinestrol-Quingestanol.

1: 137,

1970.

3.

Guiloff,

E.,

Berman,

Clinical

C.W.:

estrol-Quingestanol

4.

McKee,

Lotvin,

Vol.

a.

5:131,

M.,

Tietze,

C.:

and

Berman,

21~110,

J.J.,

Lloyde, Quin-

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Soberon,

E.,

J.

and

Berman,

E.:

Quinestrol-Quin-

(Eds.

Soberon,

Fertil.

Sobrero,

A. J.

&

in Family York,

and Calderon,

20:884,

Once-a-month

35:923,

Recommended Planning,

N.Y.,

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April

J.J.:

1969.

contraceptive:

& Gynecology

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J.,

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Analysis.

Population

Lippes, ceptive

Osorio, oral

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Berman,

and Quingestanol

for Data The

Calderon,

contraceptive.

B.R.

A.,

Sterit.

in Planned

Adv. C.),

Maqueo-Topete,

estrol

7.

Fertil.

M.,

A pill-a-month

6.

Montiglio,

study of a pill-a-month

gestanol .

5.

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Maqueo-Topete, Clincial

E.,

study of a once-a-month

Quin1970.

Procedures

18 (Supplement).

1967.

A five year comparison of the contmJ. and Feldman, J.G.: rates between women using Loop D and oml contraceptives.

Contraception

3:313,

1971

ACKNOWLEDGEMENT This study was supported Lambert

42

by grants

from The Ford Foundation

and the Warner-

Company.

JULY

1973

VOL.

8 NO.

1