Am

J Psychiatry

Opiate

137:8,

Use

BY STEVEN
AND

and

opiate

909

1980

Sexual

M. MIRIN,
ELLINGBOE,

JAMES

Although

August

Function

M.D.,

ROGER

E. MEYER,

M.D.,

addicts

often

equate

the

drug

tith
sexual
orgasm
diminished
libido
and
impaired
sexual
performance
are common
sequelae
of
chronic
use. Early
clinical
studies
suggested
that
opiates
may interfere
with sex hormone
secretion.
The
authors
carried
out three sequential
studies
%hich
demonstrated
that heroin
use in man results
in acute
suppression
ofluteinizing
hormone
(LH) release
from
the pituitaryfollrnied
by a secondary
drop in plasma
testosterone
levels.
The time course
of these
experience

neuroendocrine

events

tension-reducing
drive reduction
reinforcement.

he dramatic
heroin
have
and users (1-4).
lowed

by

in

called
gasm,

this

sexual

terms.

and

mediate

sexual

vell

with

the

and suggests
that
component
of opiate

effects
produced
by an injection
of
been well described
by both clinicians
A briefbut
very intense
euphoria,
fol-

tension

nominator

correlates

effects
ofheroin
is an important

relief,

the

sequence
addicts

seems

heroin

postinjection

and

to be

experience.

of events
themselves

In the case

orgasm,

the

the

common

de(5)

Chessick
pharmacogenic

often

of intravenous

rush

is frequently

subsequent

feelings

heroin

the im-

equated

132nd annual meeting

ofthe American
PsychiatChicago,
Ill., May 12-18, 1979. Received
May 21,
July 26, 1979.
From
the
Department
of Psychiatry,
Harvard
Medical
School
(Drs. Mirin and Mendelson),
the Psychopharmacology
Service
Outpatient
Department
(Dr. Mirin),
and the Alcohol
and Drug Abuse
Research
Center
(Dr. Mendelson),
McLean
Hospital,
Belmont,
Mass; the Department
of Psychiatry,
University
of Connecticut
School
of Medicine,
Farmington,
Conn. (Dr. Meyer);
and the Dcpartment
of Biochemistry,
Harvard
Medical
School,
Boston,
Mass.
(Dr. Ellingboe).
Address
reprint
requests
to Dr. Mirin,
McLean
Hospital,
Belmont,
Mass. 02178.
This work was supported
by grant DA-00257
from the National
Institute
on Drug Abuse,
contract
HSM-42
from the National
Institute of Mental
Health,
and grant DA-RGO1O
from the Special Office
for Drug Abuse Prevention.
Copyright
1980 American
Psychiatric
Association
0002-953X1
80/08/0909/07/$00.50.

at the

MENDELSON,

M.D.,

In contrast
to these
retrospective
accounts
of the
drug experience,
untreated
male heroin
addicts
and
patients
in methadone
maintenance
programs
report
that decreased
interest
in sex, impotence,
and delayed
ejaculation
are common
problems
during
opiate
Use
(6-10),
and opiate withdrawal
has been associated
with
renewed
sexual interest
and premature
ejaculation
(11)
in many
patients.
As a result
of these
observations,
interest
in the sexual sequelae
of opiate use has shifted
from an emphasis
on intrapsychic
factors
to the study
of the hormonal
correlates
of drug administration.
In
this context,
a series of clinical
and laboratory
studies
have explored
the effects
of opiates
on the hypothalamic-pituitary-gonadal
axis. This paper reviews
a number ofthese
studies
in man, including
some recent
data
from our laboratory.
We will attempt
to reconcile
the
curious
dichotomy
between
the acute
reinforcing
effects

of opiates,

gratification,
chronic
use,
ing.

as expressed

and
which

in the

language

the
neuroendocrine
appear
to be somewhat

of sexual

sequelae
of
less gratify-

EFFtCTS
OF CHRONIC
PITUITARY-GONADAL

OPIATE
FUNCTION

USE ON
IN MAN

to

of tension

Presented

H.

orit in

describe

relief
and
relaxation
have
been
likened
to
being
wrapped
in warm cotton,
returning
to the womb,
or similar
allusions
to warmth,
security,
and being
cared for.

ric Association,
1979; accepted

JACK

M.D.

Early clinical
studies
use on pituitary-gonadal
variety
of methodologic

(12-14)
of the effects
of opiate
function
were hampered
by a
problems.
In outpatient
stUdies it was difficult
to control
for the amount
of prior
drug use across
subjects
as well as the amount
of time
elapsed
between
drug administratiOn
and hormonal
measurements.
Furthermore
the pituitary
gonadotropins

and

testosterone

are

secreted

in a pulsatile

fash-

ion; thus even individuals

with normal
gonadal
function have considerable
moment-to-moment
variation
in the mean plasma
level of these hormones
(15).
Consequently
the infrequent
plasma
sampling
(i.e., once or
twice per day) that characterized
earlier
clinical
studies

made

changes

it difficult

in the

episodic

to

accurately

secretory

assess

drug-induced

pattern

of these

hor-

mones.
Finally,
most early studies
lacked
the methodology for direct measurement
of pituitary
and gonadal
hormones.
More
recent
studies
(16-21)
have
used
modern
radioimmunoassay
techniques
for the quantitation
of these hormones.
In the face of these methodologic
difficulties
it is not
surprising
that
the results
of earlier
studies
often

910

OPIATE

USE

AND

SEXUAL

FUNCTION

Am

proved
contradictory.
Nonetheless
some
general
trends
can be discerned.
Azizi
and associates
(12)
found
lower than normal
levels of serum testosterone
in 8 of 16 heroin addicts
and 2 of6 chronic
methadone
users,
although
levels ofestradiol,
luteinizing
hormone
(LH),
and follicle-stimulating
hormone
(FSH)
were
not consistently
altered
in these
subjects.
Cushman
(13) also reported
no change
in LH secretion
among
active
heroin
users and abstinent
former
addicts.
In a
subsequent
study (14), however,
high dose methadone
users (>40 mg/day)
and some untreated
heroin addicts
had low plasma
testosterone
levels
when
compared
with nonaddict
controls;
they also reported
a variety
of sexual
problems
during
active drug use. In another
study,
Martin
and associates
( 16) observed
decreased
plasma
LH and FSH levels in 5 men maintained
on 100
mg of methadone
per day, but after 1 month
of abstinence
their
gonadotropin
levels
were
actually
increased
over predrug
levels.
In 1975 Mendelson
and
associates
(17) studied
a group
of patients
on heroin
maintenance
who, after receiving
fixed doses of heroin
at fixed intervals,
reported
diminished
interest
in sex
and potency
problems
and had a significant
decrease
in
plasma
testosterone
compared
with normal
nonaddict
control
subjects.
These
investigators
also found lower
than normal
levels of plasma
testosterone
in untreated
heroin
addicts
who had a recent
history
of heavy
use
and in patients
on high dose (80-150
mg/day)
methadone
maintenance.
In a subsequent
study (18) Mendelson
and Mello
found
diminished
plasma
testosterone
levels in a group ofchronic
heroin users;
after 1
month
of abstinence,
however,
their testosterone
1evels were within
the normal
range for adult males.
Finally, Cicero
and associates
(19) compared
29 patients
maintained
on methadone
(mean
dose=67
mg/day)
with 16 active
heroin
addicts
and 43 drug-free
controls
and
found
that
methadone-treated
patients
had
markedly
impaired
function
of their secondary
sex organs and significantly
lower levels of serum
testosterone compared
with the other two groups.
Over the last 4 years our research
group has carried
out a series of studies
on the acute and chronic
effects
of opiate
administration
on pituitary-gonadal
function,
attempting
to avoid
some of the methodologic
problems
found
in earlier
studies.
As part of a multidisciplinary

research

project,

detoxified

heroin

addicts

were
admitted
to a four-bed
research
ward
and allowed
to self-administer
intravenous
heroin
under
a
variety
of experimental
conditions.
Their
informed
consent
was obtained
after the procedures
had been
fully explained.
In all studies
individual
subjects
or
groups
of subjects
served
as their own controls.
Heroin dosage
and the timing
of plasma
sampling
for hormonal
determinations
was controlled
by the experimenters.
Since
these
studies,
including
the methods
used to quantitate
plasma
levels
of testosterone
and
pituitary
gonadotropins,
have been reported
elsewhere
(20-22),
we will only summarize
our findings
here. The

designs
table

of

our

three

J Psychiatry

experiments

/37:8, August

are

1980

presented

in

1.

Experiment

In our first study

(20) we assessed
the effects
of
chronic
heroin
use on plasma
testosterone
levels in 10
detoxified
addicts,
who were permitted
self-regulated
access
to increasing
doses of intravenous
heroin over a
10-day period.
Blood samples
for plasma
testosterone
determinations
were collected
each morning
at 8 a.m.,
approximately
6 hours after the previous
heroin
injection. The acute hormonal
response
to heroin
or its effect on pituitary
gonadotropins
was not assessed
in
this

first

study.

During

study

period

2, as the

total

daily

dose of heroin
increased,
plasma
testosterone
levels
fell. When
the preceding
days
heroin
dose was between 45 and 60 mg, testosterone
levels fell below 400
ng/lOO ml, significantly
lower than during study period
1 when
subjects
were
drug-free
(p<.02,
matched
t
test). Following
a period
of methadone
detoxification
(study
period
3), testosterone
secretion
gradually
returned
to predrug
levels.
,

Experiment

In our second
study (21) we sought
to measure
the
acute
effects
of heroin
on the pituitary-gonadal
axis.
After 2 weeks on a drug-free
regimen
and 1 saline control day (periods
1 and 2), 2 detoxified
male addicts
were given
10 mg i.v. of heroin.
The 2 subjects
had
very similar
hormonal
responses.
As illustrated
in figure 1 (subject
1) the result
was an almost
immediate
fall in the level ofplasma
LH. This acute response
was
not observed
when subjects
received
saline,
nor did it
occur when subjects
were pretreated
with naltrexone,
a narcotic
antagonist
with few agonistic
effects
of its
own (23). In both subjects
LH suppression
was still
observed
6 hours after heroin
injection,
although
some
recovery
in LH secretion
was noted in 1 subject.
Interestingly,
pretreatment
with naltrexone,
12 hours
before heroin administration,
resulted
in a mean 50% rise
in plasma

LH

levels

compared

control
day. The number
tory pulses also increased
istration.

Despite

the

rise

with

levels

on the

saline

and frequency
of LH secrefollowing
naltrexone
adminin LH,

however,

testoster-

one secretion
was only marginally
increased
in 1 subject
and unaffected
in the other.
In none
of the
experimental
conditions
was FSH affected.
Experiment

In our third study

(22) we examined
the acute
and
chronic
effects
of unblocked
and naltrexone-blocked
heroin
use on the pituitary-gonadal
axis.
Our goals
were
to replicate
our findings
from experiment
2 in
more subjects
and to better
assess
the time course
of
the acute suppressant
effect of heroin
on LH and testosterone.
We also
wanted
to determine
whether
chronic
heroin
and/or
naltrexone
use altered
the acute
response
to heroin.
There
were three different
double-

Am

J Psychiatry

137:8,

FIGURE 1
Plasma Testosterone,

100

OO

1980

MIRIN,

LH, and FSH Levels Before and After Injection

Day

August

(2 cc iv.)

14-Saline

Day

of Saline,

Heroin,

15-Heroin

(10

MEYER,

MENDELSON,

and Heroin Preceded

by Naltrexone
19-Heroin

Day

mg iv.)

ET

hours

after

AL

911

(22)a

(10 mg iv.)

12

(50

naltrexone

mg

w
0

700-

cbA/AJ

00

500S

300-

300

200

Id-c_I

1-c:.5-1

I
2

r1::1..I

Ij.I

1U

1Oi
300-

IU)
Li.

21

56

I1?1

BEFORE

HOURS

&All injections

TABLE

were

given

123456
OR AFTER

c.E?1

#{149} 1-I--

12345

INJECTION

at 10:00 am.

Three Studies

of

the Acute and Chronic

Experiment

Study

1 (N=

Day

Period

Effects of Opiate

1-7
8-17

Drug-free
Heroina

18-24

Methadone

on Pituitary-Gonadal

Expe riment

10)

Condition

1
2

Administration

Experi

Condition

1-13
l4(lO:OOa.m.)
15 (10:00

(22)

2 (N=2)

Day

detoxification

Function

a.m.)

Drug-free
Saline,2mli.v.
Heroin,

ment

3 (N =8)

Day

Condition

1-7
7(2p.m.)

10 mg iv.

Drug-free

Heroin, l0mgi.v.
(unblocked)

10 (6 p.m.)
10 (10 p.m.)

(unblocked)

Naloxone,
Naltrexone,
i.v.,

25-34

Drug-free

35-36

Narcotic

18 (6 p.m.)

antagonist

19(10

a.m.)

Naloxone,
Naltrexone,
Heroin,

0.4 mg iv.
50 mg p.o.

11 (2 p.m.)

12-23

10 mg iv.

7
aHeroin

8 to

5
6 hours

Narcotic
antagonist
plus heroin

37-46

20-25

(8 a.m.)

P.O.,

Naltrexone,

50 mg

p.o.

13 (10 a.m.)

or placebo

Heroina

to 23 (8 a.m.)
23 (2 p.m.)
Heroin,
10 mg i.v.
Narcotic
antagonist
alone
was available
any time but not more often than every 2 hours to prevent drug accumulation.
The allowable intravenous
dose escalated from 0.5 mg on day
mg on day 18 to accommodate
tolerance. By waiting 4 hours the subject
could
double
the allowable dose; after 6 hours he could triple it. Waiting longer than
resulted
in no further
increment.
Subjects had the option of not self-administering
heroin or of taking less than the allowable dose.
47-60

blind conditions.
After 6 drug-free
days 8 subjects
received
an injection
of 10 mg of heroin;
4 days later all
subjects
received
intravenous
saline
12 hours
after
pretreatment
with
either
naltrexone
(N4)
or an
equivalent
volume
of placebo
(N=4).
After 10 days of
access
to heroin
(see table
1) naltrexone-treated
and
placebo-treated
subjects
received
another
10-mg dose
of heroin.
Plasma
levels of LH and testosterone
were
determined
on integrated
blood
samples
collected
at
30-minute

after
with

or placebo

Saline, 2 ml i.v.,
plus naltrexone,
50
mgp.o.,
or placebo
Naltrexone,
50mg

(blocked)
6

0.4 mg i.v.
50mg

intervals

from

4 hours

before

to

each test injection.

Blood samples
were
the use of a constant
exfusion
pump;

10 hours

collected
thus hor-

monal

levels

30-minute

In general,
sistent

are expressed
collection

with

pooled
our

as the mean

value

for each

period.
earlier

data

for these
findings.

subjects
As

illustrated

were

conin the

top panel of figure 2 heroin-induced

suppression
of LH
secretion
was first evident
2-4 hours and was greatest
4-6 hours
after
unblocked
heroin
injection.
In this
study the degree
of LH suppression
was not as great as
that observed
previously.
Since
some
subjects
were
given heroin
after only 1 week on the research
ward,
compared
with a 2-week
drug-free
period
in the earlier
studies,
some may have been partially
tolerant
to the

912

OPIATE

USE

AND

SEXUAL

FIGURE
2
Effects of Heroin (10 mg i.v.) Versus
of LH and Testosterone (22)

Am

FUNCTION

Isotonic

Saline

on Plasma

Levels

J Psychiatry

/37:8, August

1980

FIGURE
3
Effects of Heroin (10 mg i.v.) Versus Isotonic Saline on Plasma Levels
of LH and Testosterone on Day 1 1 (Before Heroin Phase) (22)
Naltrexone

LI

plus saline (N =4)

Placebo plus salIne (N =4)

100],

IErrIiFE
4

0-2

2-4

4-6

6-8

8-10

Naltrexone
1400

LIIPlacebo

plus saline (N =3)

plus saline (N =4)

1200-1
I

(I)
-

I
I

-o

<0

Q-

aln the unblocked

8 subjects;

all

heroin condition,
injections

were

given

accurate

data were obtained

at 2:00

in

6 of the

600-

<
uJ

I
I

p.m.

0-2

effects
of heroin
on LH. The maximum
decline
in
plasma
testosterone
occurred
6-8 hours
after heroin
injection
(bottom
panel figure 2). As in experiment
2,
some recovery
in LH secretion
was noted 6 hours after
heroin
injection
and was followed
shortly
by a rise in
plasma
testosterone.
As illustrated
in figure 3 measurement
of plasma
LH
in

subjects

on

naltrexone

or

placebo

also

replicated

our earlier
finding-the
naltrexone-treated
subjects
had consistently
higher
levels of LH, but their plasma
testosterone
levels were no different
from the placebotreated
group.
After 10 days of unblocked
heroin
use,
there was some indication
that tolerance
developed
to
the drugs
acute
suppressant
effect on LH and testosterone,
but the timing ofdrug
administration
and blood
sampling
in this study
did not allow for accurate
assessment
of this question.
Investigation
of tolerance
development
would
require
that
the hormonal
response
to a single dose of heroin
be measured
on several consecutive
days
during
a sustained
period
of
fixed-dose,
fixed-interval
drug administration.

DISCUSSION

Opiate

Effects

on Sexual

Functioning

There
is ample
clinical
evidence
that sexual
drive
and performance
are diminished
in male opiate
addicts
(6-11).
Only recently,
however,
has a link been forged
between
these
clinical
observations
and opiate-induced
changes
in the hypothalamic-pituitary-gonadal

aAccute

data

on plasma

4-6

2-4

HOURS

BEFORE

testosterone

levels

naltrexone-treated

subjects;

all injections

axis.

animal

studies

Recent

6-8

OR AFTER
were

8-10

INJECTION
obtained

in 3 of the

were given at 2:00 p.m.

(24-26)

and

our

data

in

man (2 1 , 22) suggest

that
a prominent
neuroendocrine
effect ofopiate
administration
is suppression
of plasma
LH secretion
followed
by a secondary
decline
in testosterone
production.
If the primary
effect of heroin
were on testosterone
biosynthesis
or metabolism,
we
would
have expected
a more rapid fall in plasma
testosterone
followed
by an increase
in plasma
LH. This
is the

normal

response

to

a fall

in plasma

testosterone

and results
from disinhibition
of the tonic control
exerted by testosterone
on the release
of luteinizing
hormone releasing
factor
(LRF)
from the hypothalamus.
LRF is released
in episodic
bursts
and, in turn, controls
LH secretion
from the pituitary
(27-29).
That
acute heroin
administration
appears
to completely
inhibit episodic
LH secretory
pulses
suggests
a central
effect on the release
of hypothalamic
LRF.
In laboratory animals
the regulation
of LH (via LRF secretion)
has been localized
to ventral
and medial
areas
of the
hypothalamus
(30), a region
that also possesses
numerous
opiate
receptor
binding
sites and a high concentration
of endogenous
opiate
peptides
(31).
In our studies
pretreatment
with a narcotic
antagonist
(naltrexone)
not
only
blocked
heroin-mediated
suppression
of LH release
but actually
increased
the
frequency
of LH secretory
bursts
from the pituitary.
As a result
mean
plasma
LH levels
were elevated
in
naltrexone-treated
subjects.
This finding
can best be

Am

J Psychiatry

explained

in

137:8,

light

of

August

our

/980

MIRIN,

advancing

knowledge

about

the role of endogenous

opioids
(i.e., endorphins)
and
opiate
receptors
in the regulation
of hormonal
output.
The endogenous
opioids
may play an inhibitory
role in
the normal
regulation
of LH secretion
(32), and this
inhibitory
effect may be blocked
by administration
of a
narcotic
antagonist.
One could
also explain
naltrexones
stimulation
of LH release
as a hormonal
concomitant
of precipitated
abstinence;
however,
a recent
double-blind
study by Ellingboe
and associates
(33) revealed
that naltrexone
given to nonaddicts
increased
mean plasma
LH levels
by 50% over baseline,
which
again suggests
the involvement
of a hypothalamic-pituitary
mechanism.
Finally,
our studies
indicated
little effect of either
heroin
or naltrexone
on plasma
FSH secretion.
Cicero
and associates
(24, 25) found
the same dichotomous
response
to opiates
in the rat. Their data suggest
that
those
areas of the hypothalamus
which
influence
the
synthesis
sensitive

and release
to the effects

of pituitary
of opiates

LH
than

may
be more
those
which
me-

diate
FSH
levels.
Although
one study
has demonstrated
anatomic
separation
of the centers
that control
LH and FSH release
in animals
(34), there is no clear
evidence
of such
a separation
in man.
Indeed,
the
decapeptide
(LRF)
that regulates
pituitary
release
of
LH probably
plays a role in FSH release
as well, although
the pituitary
response
is usually
of lower magnitude.
Correlation

ofEndocrine

Changes

with

Mood

States

Addicts
often
cite the acute euphorigenic
and tension-relieving
effects
of opioids
as important
factors
in
the decision
to initiate
and maintain
drug use. At the
same
time,
laboratory
studies
of opiate
use in man
have consistently
demonstrated
that chronic
administration
of these substances
is associated
with the development
of increased
psychopathology
and dysphoric mood

states

(35-38).

Recently

we

have

attempted

to

relate
such events
to changes
in brain catecholamine
levels
(39), but the observed
clinical
phenomena
are
the result
of many
factors,
including
expectancy
and
the setting
in which
the data are gathered.
At present
there
are also sufficient
data to explain
the
rush

brief
that

(30-60
seconds)
but
intensely
immediately
follows
intravenous

pleasurable
heroin
ad-

ministration.
The
mechanism
most
likely
involves
massive
release
of catecholamines
at both central
and
peripheral
sites. The rush is followed
by a less intense,
but more sustained,
period
of relaxation
and tension
relief lasting
2-4 hours.
The strength
and duration
of
this effect are influenced
by the dose administered,
the
level of plasma
morphine
achieved
(heroin
[diacetylmorphine]
is almost
immediately
converted
to morphine by the liver), the rate of elimination
of the drug,
the degree
of tolerance
developed,
and the conditioned
and unconditioned
stimulus
properties
of the environment (39-40).
The time course
of this effect closely

MEYER,

MENDELSON,

ET

AL

913

parallels,
and may be related
to, the acute
effects
of
heroin
on neuroendocrine
function-specifically,
the
acute suppression
of LH release
followed
by a secondary fall in plasma
testosterone.
Indeed,
heroin
acts
much
like the antiandrogen
compound
cyproterone
acetate,
which
suppresses
the release
of pituitary
gonadotropins
(especially
LH), lowers
testosterone
1evels, and reduces
both sexual
drive
and performance
(41). In low doses
acute administration
of cyproterone
acetate
alters the computerized
electroencephalogram
in a fashion
similar
to that of the tricyclic
antidepressants; larger doses produce
a profile much like the benzodiazepine
anxiolytics
(42). On the other
hand,
as
with
heroin,
chronic
administration
of cyproterone
acetate
has been reported
to produce
apathy,
restlessness, and depression
(41). The similarity
of these data
to our observations
in heroin
users is striking.
In contrast,
acute
administration
of naltrexone
raises
LH
levels in detoxified
opiate
addicts
(21) and normal
volunteers
(33), while producing
a dysphoric
mood state
and increased
sexual
drive (43).
Although
no direct
link has been demonstrated
between
sex hormone
changes
and temporally
related
alterations
in mood,
our data on the acute effects of heroin suggest
a drive
reduction
model
of opiate
reinforcement,
in which
the drug acts as an antianxiety
agent and reduces
sexual
drive and tension.
Whether
this

effect

is a direct

consequence

of acute

suppression

of LH and testosterone
or is mediated
through
the
same
hypothalamic
mechanisms
that control
LH release (i.e., alterations
in catecholamine
systems)
is unclear. It is also possible
that changes
in other hormone
systems
(e.g. , the hypothalamic-pituitary-adrenal
axis)
may also play a role.
With repeated
heroin
use, tolerance
develops
to the
drugs acute positive
effects on mood (38) and subjects
manifest
increasing
apathy,
irritability,
depression,
and social withdrawal
(38, 40). This may be related
to
the development
of tolerance
to its acute
suppressant
effect on LH and testosterone
or to alterations
in the
catecholamine
systems
that control
mood
and hormonal
output.
Nonetheless,
chronic
heroin
users and
patients
on high doses of methadone
still have low circulating
levels of testosterone,
a condition
common
to
other groups
who manifest
high levels of anxiety
and
depression,
such as soldiers
under
stress
(44, 45), intoxicated
alcoholics
(46), and monkeys
who have recently
lost status
(47). Although
there are data which
suggest
that testosterone
may exert a mood-elevating
effect in man (48, 49), Sachar
and associates
(50) found
no correlation
between
testosterone
levels and mood.
The relationship
between
the subjective
effects
of
opiate
use and the neuroendocrine
events
that accompany these phenomena
is still unclear.
We do not yet
understand
the role of endorphins
in the regulation
of
sex hormone
secretion,
the mediation
of drive states,
and the regulation
of mood.
We hope that future
research
will help to clarify
these issues.

914

OPIATE

USE

AND

SEXUAL

FUNCTION

Am

REFERENCES

27.

1. Rado 5: Psychoanalysis
of pharmacothymia
Psychoanal
Q 2:1-23,
1933
2. Khantzian
E: Opiate
addiction:
a critique
implications
for treatment.
Am J Psychother
3.

4.
5.
6.
7.

8.
9.

Wurmser
compulsive
Savit
RA:

ence

of theory
and some
28:59-70,
1974
L: Psychoanalytic
considerations
of the etiology
of
drug use. J Am Psychoanal
Assoc 22:820- 843, 1974
Psychoanalytic

methadone,

13.

14.
15.

16.
17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

studies

in Proceedings

on Methadone

ment Printing
10. Bloom

12.

addiction).

on addiction:

ego structure

Office,

Treatment.

of the Third

National

Washington,

DC,

28.

in

narcotic
addiction.
Psychoanal
Q 32:43-57,
1963
Chessick
RD: The pharmacogenic
orgasm
in the drug addict.
Arch Gen Psychiatry
3:545-556,
1960
Mathis JL: Sexual aspects
of heroin addiction.
Medical
Aspects
of Human
Sexuality
4:98, 1970
Garbutt
G, Goldstein
A: Blind comparison
of three methadone
maintenance
dosages
in 180 patients,
in Proceedings
of the
Fourth
National
Conference
on Methadone
Treatment.
New
York, National
Association
for Prevention
of Addiction
to Narcotics,
1972
Cushman
P, Dole V: Detoxification
of rehabilitated
methadone
maintained
patients.
JAMA 226:747-752,
1973
Wieland W, Yunger M: Sexual effects and side effects of heroin
and

11.

(drug

29.

30.

3 1.
32.

Confer-

US Govern-

1970

W, Butcher
B: Methadone
side effects and related symptoms in 200 methadone
maintenance
patients.
Ibid
Mintz J, OHare
K, OBrien CP, et al: Sexual problems
of heroin addicts.
Arch Gen Psychiatry
31:700-703,
1974
Azizi F, Vagenakis
AG, Longcope
C, et al: Decreased
serum
testosterone
concentration
in male heroin
and methadone
addicts.
Steroids
22:467-472,
1973
Cushman
P Jr: Sexual
behavior
in heroin addiction
and methadone maintenance.
Correlation
with plasma
luteinizing
hormone. NY State J Med 72:1261-1265,
1972
Cushman
P Jr: Plasma
testosterone
in narcotic
addiction.
Am J
Med 55:452-458,
1973
Dc Lacerda
L, Kowarski
A, Johanson
AJ, et al: Integrated
concentration
and circadian
variation
of plasma testosterone
in normal men. J Clin Endocrinol
Metab 37:366-370,
1973
Martin
WR, Jasinski
DR, Haertzen
CA, et al: Methadone-a
reevaluation.
Arch Gen Psychiatry
28:286-295,
1973
Mendelson
JH, Mendelson
JE, Patch VD: Plasma
testosterone
levels
in heroin
addiction
and during methadone
maintenance.
J
Pharmacol Exp Ther 192:211-217,
1975
Mendelson
JH, Mello NK: Plasma testosterone
levels during
chronic
heroin
use and protracted
abstinence.
Clin Pharmacol
Ther 17:529-533, 1975
Cicero TJ, Bell RD, Wiest WG, et al: Function
of the male sex
organs
in heroin
and methadone
users. N EngI J Med 292:882887, 1975
Mendelson
JH, Meyer RE, Ellingboe
J, et al: Effects of heroin
and methadone
on plasma
cortisol
and testosterone.
J Pharmacol Exp Ther 195:296-302,
1975
Mirin SM, Mendelson
JH, Ellingboe
J, et al: Acute effects of
heroin
and naltrexone
on testosterone
and gonadotropin
secretion: a pilot study.
Psychoneuroendocrinology
1:359-369,
1976
Mirin SM, Meyer RE, Ellingboe
J, et al: The effects of opiates
on neuroendocrine
function,
in The Heroin
Stimulus.
By Meyer
RE, Mirin SM. New York, Plenum
Press,
1978
Martin
WR, Jasinski
DR. Mansky
PA: Naltrexone,
an antagonist for the treatment
of heroin
dependence:
effects
on man.
Arch Gen Psychiatry
28:784-791
,
1973
Cicero
TJ, Wilcox
CE, Bell RD. et al: Acute
reductions
in
serum
testosterone
levels
by narcotics
in the male rat: stereospecificity,
blockade
by naloxone,
and tolerance.
J Pharmacol
Exp Ther 198:340-346,
1976
Cicero TJ, Bell RD, Meyer ER, et al: Narcotics
and the hypothalamic-pituitary-gonadal
axis: acute effects on luteinizing
hormone,
testosterone
and androgen-dependent
systems.
J Pharmacol Exp Ther 200:76-83, 1977
Cicero TJ, Badger
TM, Wilcox CE, et al: Morphine
decreases
luteinizing
hormone
by an action on the hypothalamic-pituitary
axis.
J Pharmacol
Exp Ther 203:548-555,
1977

33.

J Psychiatry

137:8, August

1980

McCann
SM: Regulation
of secretion
of follicle-stimulating
hormone and luteinizing
hormone,
in Handbook
of Physiology
5cction 7: Endocrinology.
The Pituitary
Gland, vol 4, part 2. Edited
by Astwood
EB, Greep RO. Bethesda,
Md, American
Physiological Society,
1974
Cannel
PC, Araki 5, Fern
M: Pituitary
stalk portal blood collection
in rhesus
monkeys:
evidence
for a pulsatile
release
of
gonadotropin-releasing
hormone.
Endocrinology
99:230-248,
1976
Neill JD, Patton JM, Dailey RA, et al: Luteinizing
hormone
releasing hormone
(LHRH)
in pituitary
stalk blood of rhesus monkeys:
relationship
to level
of LH release.
Endocrinology
101:430-434, 1977
Blake CA, Sawyer
CH: Effects of hypothalamic
deafferentation
on the pulsatile
rhythm
in plasma
concentrations
of luteinizing
hormone
in ovariectomized
rats. Endocrinology
94:730-736,
1974
Snyder SH : Opiate
receptor
in normal
and drug altered
brain
function.
Nature
257: 185-189,
1975
Simantov
R, Snyder
SH: Brain-pituitary
opiate mechanisms:
pituitary
opiate
receptor
binding,
radioimmunoassay
for methionine enkephalin
and leucine
enkephalin,
and f3-H-enkephalin
interactions
with the opiate
receptor,
in Opiates
and Endogenous
Opioid
Peptides.
Edited
by Kosterlitz
H. Amsterdam,
North Holland
Elsevier,
1976
Ellingboe
J, Mendelson
JH, Holbrook
PG, et al: Naltrexone
effects on luteinizing
hormone
(LH) secretion
and mood states
implicate
endogenous
opioid mechanism
in regulation
of the hypothalamic-pituitary-gonadal
axis (abstract).
Fed Proc 37:275,
1978

34.

Bishop

W, Kalra

PS,

of hypothalamic

in response

prolactin

female
35.

Fawcett

lesions

rats.

CP,

Krulich

on the release

to estrogen

Endocrinology

and progesterone

91:1404-1410,

Wikler

A: A psychodynamic

mental

self-regulated

readdiction

L, et al: The effects

of gonadotropins

and

treatment

in

1972

study of a patient
during
to morphine.
Psychiatry

experiQuar-

terly 26:270-293,
1952
Haertzen
CA, Hooks NT: Changes
in personality
and subjective
experience
associated
with the chronic
administration
and withdrawal of opiates.
J Nerv Ment Dis 148:606-614,
1969
Mirin SM, Meyer
RE, McNamee
HB: Psychopathology,
craying, and mood during
heroin acquisition.
mt J Addict 11:525-

36.

37.

544, 1976

Mirin

SM, Meyer RE: Psychopathology

and mood during heroin
in The Heroin
Stimulus.
By Meyer
RE, Mirin SM. New
York, Plenum Press,
1978
Meyer
RE, Schildkraut
JJ, Mirin SM, et al: Opiates,
catecholamines,
behavior
and mood. Psychopharmacology
56:327333, 1978
Babor TF, Mirin SM, Meyer RE: Behavioral
and social effects

38.

use,

39.

40.

(of heroin),
41

42.

43.

in The Heroin

Stimulus.

By Meyer

RE, Mirin SM.

New York, Plenum

Press,
1978
Cooper
AJ, Ismail AAA, Phanjoo
AL, et al: Antiandrogen
(cyproterone
acetate)
therapy
in deviant
hypersexuality.
Br J Psychiatry
120:58-64,
1972
Itil TM: Neurophysiological
effects
of hormones
in humans:
computer
EEG profiles
of sex and hypothalamic
hormones,
in
Hormones,
Behavior
and Psychopathology.
Edited
by Sachar
EJ. New York,
Raven
Press,
1976
Mendelson
JH, Ellingboe
J, Kuenle
J, et al: Effects
of naltrex-

one

on mood

and

neuroendocrine

function

in normal

adult

males.

44.

45.

46.
47.

Psychoneuroendocrinology
3:231-236,
1979
Rose RM, Bourne P0, Poe RO, et al: Androgen
responses
to
stress:
II. Excretion
of testosterone,
epitestosterone,
androsterone
and etcocholanolone
during basic combat
training
and
under threat of attack.
Psychosom
Med 31:418-436,
1969
Kreuz LE, Rose RM, Jennings
JR: Suppression
of plasma
testosterone
levels and psychological
stress: a longitudinal
study of
young men in Officer
Candidate
School.
Arch Gen Psychiatry
26:479-482,
1972
Mendelson
JH, Mello NK: Alcohol,
aggression,
and androgens.
Res Publ Assoc Res Nerv Ment Dis 52:225-247,
1974
Rose

conflict

RM,

Bernstein

on plasma

IS,

Gordon

testosterone

TP:

levels

Consequences

in rhesus

of

monkeys.

social

Psy-

Am

J Psychiatry

chosom
48.

49.

Med

/37:8, August

37:50-61,

EL, Broverman
hormones
in depression,
Psychotropic
Hormones.
Klaiber

1980

MIRIN,

mann WM. Holliswood,

NY, Halstead
Press,
1976
Itil TM, Cora R, Akpinar
5, et al: Psychotropic
action

ET

915

AL

in establishing
the immediate
Curr Ther Res 16:1147-1170,

1974

50.

Sachar

EJ, Halpern

testosterone

of sex

MENDELSON,

hormones:
computerized
EEG
CNS effects of steroid hormones.

1975

DM, Vogel W, et al: The use of steroid

in The Proceedings
of the Meeting on
Edited by Itil T, Laudahn
G, Herr-

MEYER,

28:15-18,

levels

1973

F, Rosenfeld
in

depressed

RS, et al: Plasma

men.

Arch

Gen

and urinary
Psychiatry