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0022-202X/79/ 7301-0108$02.00/0

TH E

JOURNAL

OF INVESTIGATIVE DERMATOLOGY, 73:108-111,1979

Copyright 1979 by The Williams Wilkins Co.

Vol.

73

, NO.1

Printed

ill

U S .A

Age related Changes in Sebaceous Gland

Activity

PETER

E.

POCHI, M .D., JOHN S. STRAUSS, M.D. , AND DONALD T DOWNING, PH.D.

Department

of

Dermatology University Hospital Boston Mass. U.S.A.

The sebaceous glands

of man

show age

-

related

differ

ences

in their

activity as determin ed

by

quantitative and

qualitative

examination

of sebum. Sebaceous

secretion

is low

in

children and begins to increase

in

mid

-

to late

childhood

under the

influence

of androgens. This rise

continues until

the late

teens,

after

which

no further

significant change takes place until

late

in

life.

In elderly

men,

sebum levels remain essentially un-

changed from

those of

younger adults until the age of

80. In

women, sebaceous secretion decreases gradually

after

menopause

and

shows no

significant change after

the

7th

decade. The most likely

explanation

for the de -

crease

in

sebaceous gland secretion with age

in

both

men and women is

a

concomitant decrease

in the endog-

enous

prod.uction

of

androgens.

Although surface lipid

levels

fall with

age,

paradoxi

cally

the sebaceous'

glands

become larger,

rather than

smaller, as a

result

of decreased

cellular

turnover.

None-

theless,

as the higher surface lipid

levels

after adminis-

tration

of fluoxymesterone

(a synthetic

testosterone

de -

rivative)

indicate, the glands have the

capacity

to re-

spond

to

androgens.

Sebaceous gland activity decreases with advancing age l l

The principal cause for this attrition appears to be diminished

hormonal

stimulation,

a

reversal

of the increase in glandular

activity that occurs

at

puberty through augmented elaboration

of androgenic steroids. This review is concerned with studies

on

sebaceous

gland

activity

in

the

aged

and the

correlation

of

these findings

with hormonal alterations

that occur in

late

middle age and senescence . Data are also presented

on

the

developmental changes

occurring from

the

time the glands

begin to mature to the time

they

reach

their

adult

state

.

METHODS

In our laboratories, sebaceous gland activity

is

measured

by

a method

[2]

that involves the absorption of surface lipids from a defined area of

the forehead onto absorbent papers for a period of 3 hr. The lipids

collected are extracted

by

ether and measured gravimetrically. The

determination of individuai lipid class components of forehead surface

lipids is made by thin-layer chromatographic separation and photoden

sitometric quantification [3].

SEBACEOUS GLAND

DEVELOPMENT

Human

sebaceous glands develop during fetal life between

weeks 13 and

15

of gestation; they

attain

fair size by the time of

birth

and then mostly

shrink

to comparatively small structures

during childhood [4]. With the onset of puberty and stimulation

by androgens, there is

glandular hyperplasia

and an increase in

the synthesis

and

secretion

of

sebum.

Studies

by Cotterill et al

Reprint requests to : Peter

E.

Pochi, M.D ., Department of Derma

tology, University Hospital , 75 E. Newton Street Boston, Mass. 02118.

This work was supported

by

U.S. Public Health Service grant IROI

HD11632 (National Institute of Child Health and Development).

Drs. Strauss and Downing are currently t the Department of

Dermatology, University of Iowa Hospitals, Iowa City, Iowa.

Abbreviations:

T, = thyroxine

T

=

triiodothyronine

TSH

=

thyroid-stimulating hormone (thyrotropin) .

108

comprising

cross-sectional

analyses

in

children

before

and

after

the age of 10, showed no increase in sebum secretion until

the

mid teens, except in

menarchal

girls, in whom

the

increase

was

evident somewhat earlier [5]. However, sebum production tests

we

performed

twice yearly in each of

9

boys and 6 girls for a

3-

yr period showed

an

earlier increase in

sebum

production .

Figure 1 illustrates our results. A gradual increment

in

the

amount

of

sebum

secreted

occurred; this increment became

somewhat more abrupt at

age 13. No obvious sex difference was

apparent, either in the quantity of sebum produced at any given

age

or

in

the

slope of

the

line

representing

sebum secretion.

In actuality, one can observe

an

even earlier increase in

sebaceous gland activity, before the age of 9 by determining

the

relative

composition of skin surface lipids, which are mix-

tures of sebaceous and epidermal lipids [6]. As sebum secretion

begins

to increase

in

late

childhood,

the

amount

of

wax

esters

,

which are of

sebaceous origin, increases relative to

the amounts

of

cholesterol and cholesterol esters, which are epidermal lipids.

One can show

that

the wax esters/[ cholesterol+cholesterol

esters] ratio increases

at

approximately 7

or

8

yr of

age and

these lipids approach an adult composition by age 10 or

[7,8].

Published

results of studies based on examinations

of

individ-

uals of different ages suggest

that

full sebaceous gland matu-

ration is not attained until either late in

the

2nd decade or early

in the

3rd

decade [4,5,9,10]. Figure 2 shows

data obtained

in a

13-yr longitudinal study

of

sebum secretion in 2 children, a bo y

and a girl. Sebum

production

was

measured

in each of the

children 4 times yearly. Secretion clearly increased

at

age 12

or

13,

continued

to

increase gradually

and

steadily until

age 17 or

18

and then appeared to

enter

a stable phase. Our

lack

of

evidence for an earlier sebum increase in the girl was in contrast

to

another

report [5] which indicated greater production in 11-

to 15-yr-old girls, especially menarchal ones.

SEBUM STUDIES

IN THE

AGED

Once

maturity

has been achieved, little change in sebaceous

gland

activity

takes place until

middle

age

and

thereafter . Table

I shows sebum production values in women and men 40 y or

older. Average sebum

production

levels in the women fell by

approximately

40% in the 6th decade, declined

additionally

in

the 7th decade, and

remained

constant thereafter. In the me n,

no change was observed until the 8th

decade

. At any age range

examined,

mean sebum

values

in

the men

exceeded

those

in

the women.

This

finding of a drop in surface

sebum

levels with

advancing age and of a greater decrease in women is in general

agreement

with

reports

of

other

studies [5,10-15]'

Reduced

sebaceous gland activity, as evidenced by lower surface lipid

levels, has also

been

demonstrated in vitro by diminished

formation

of squalene,

and to

a lesser extent of wax esters, from

glucose in skin biopsy samples from the backs

of

elderly men

[16]. .

Study

of

the

forehead surface lipid composition in 15 children ,

18 young

adult

women, and 10 postmenopausal women revealed

wax esters/[

cholesterol+cholesterol

esters]

ratios that

were low

in the children, high in the young adults, and low in the age d

women (Table II). These changes reflect the differences in

sebaceous

gland

activity occurring

at

these

various times

of

life.

The most probable explanation for the decrease in sebaceous

gland

synthesis

and secretion in the

aged

is a

concomitan

t

decrease in the production of androgens. In men, testosterone

7/26/2019 Age n Sebaceous Gland

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July 1979

:J

o

r::

M

E

u

cr

fJJ

o

0

'is.

::;

Ol

1 .5

1 0

0 .5

I

9 10 11

AGE (years)

12

13

FIG 1.

Seb

um

production

in

15 children tested

tw

ice yea rly over a

-yr period. Height of each co lumn represents the mean sebum va

lu

e

he results obta

in

ed

at

the age when tested.

0

=

6 g

irl

s;

=

9

bo

ys.

3 .5

3 .0

;

2 .5

2 .0

1 .5

1 .0

0 .5

I

I

- l e I \

I

Female / \ _ - ,

I

/

I

- '

I

I

...

I

/

/ menarche )

7 8 9

10

11

12 13

14

15 16 17 18 19

2 0 21

22

AGE

FIG

2. Longi tudinal study of se bum production

111

th e skin of 2

human beings. - - - = male; - - = femal

e.

I.

Se bum production values

in

normal men and women 40 yr

of

ag

e and older

W

ome

n Men

Age

No

.

M

n

Range

No .

Mean

Range

40-49

3

1 1.86

0.12-4.80

50

2.39

0.54-5.14

50

-

59

21

1.08

0.07-2.38 14

2.43

1.05-4.36

60-69

18 0.88

0.22-1.62 14

2.42

0.83-4.95

70-79

12 0.85

0.33-2.19

13

1.

69

0.63-3.

23

Milligrams of lipid per 10 cm' of skin per 3 hI .

lood levels gradually decline after the 6th decade bu t do not

ignifica ntly

until

approximat ely the age

of

70 [1

7-20

].

hormone data corr ela te we ll

with

the finding of no

in se bum product ion l

eve

ls

until

after the age

of

70

,

On

other hand , studies have indicated that the fraction of free

osterone,

the pr

es

um

ed form in

which

testo

st e

ron

e

enters

e target ce ll , de creases at an earlier age, usually between 50

nd 60 yr [18- 20]. That

sebaceous

gland activity does

not

until

a de cade or 2 lat e r attests to the ma

rk

ed sensi

ty of t he gland to e

ndog

enous androgen stimulation ,

SEBACEOUS GLANDS IN THE AGED

109

TABLE II. Com

parison

at different oges ofwax esters/

[cholesterol clwlesterol ester

s

ratios in forehead s

ur f

ace lipids

No . subjects

Ratio

Children

15

0.

35

Young adul t

18

7.47

wom en

Postmenopau

sa

l 10 1.46

women

In

women, androgen so

ur

ces for sebaceous gla nd stimulation

are the

ovary

and

adr

ena

l cortex. We had ass

um

ed previously

that

the postmena

pausa

l

decrease

in

sebum

production h

ad

been the result

of

ovarian involu tion and that the failure

of

many

subjects to reach prepubertal se

bum

l

eve

ls had been du e

to

persistent

adrenocort ical and rogen secretion [4].

However,

subseq

uent

st

udies demon

strated

th

at postmenopausal

ovari

es

r

et a

in a considerab le

androgen

synthet ic

capac

ity,

In

postmen

opausal

women,

plasma testostero

ne l

eve

ls fall

after

bilateral

oophorectomy [

21

] and are lower in postmenopausal

oop

horec

tomized wom en than in no

rmal

con tro ls [22 ]. Mo reover, the

concent ration

of testosterone

in the

ovaria

n vein exceeds that

in

the per

ipheral

blood [23,24] and increases significantly after

administration

of

human chorionic gonadotropin [24]. However,

a

dr

enocortical a

ndrog

en

secretion mu

st also decr

ease

in women

(and me

n

with age since there is a gradual decr

ease

in urinary

17-ketosteroid excretion and plasma concen trations of

dehy

droepia

ncb

'osterone (the

prin

cipal adl'enal andl 'ogen) [25-27].

Valu

es

for

these

acb'enal andl'ogens are gr

eate

r in men than in

women, and this differential persists

un

t il a

very

late age,

after

which they

closely

approach

one

anot

her [25,28,29].

Alt hough it is probable that the diminished se baceous gland

secretory ac tivity occurring in the aged ca n largely be expla

in

ed

by

concomitant

changes in an drogen levels, th e possible role

of

such

ot

her hormones as glucocorticoids a nd thyroid hor mones,

mer its consideration, There is ev idence th

at

human sebaceous

glands req uire cor tisol for their

optimal

response to ancb 'ogenic

st

imul

at

ion [30].

Thu

s, if

imp

a

ir

ed end ogenous co

rt i

coid activ

ity

were

to occur

with

ag ing, this defect might l

ead

to a

blunted

sebaceo

us gland

response

to androgens,

Studies

have shown a

dec reased clearance

rat

e of cortisol in the aged [31,32] and less

urin

ary excretion

of

17-ketogenic st eroids [27,33] a nd cortisol

metabo li tes [32], but

thes

e changes

are

n

ot marked

and

are

the

sa me for bo th sexes [33 ]. Moreover, other indicators of adre

nocort ical function, such

as

pl

as

ma cor tisol l

eve

ls, urinary free

cor tisol excretion ,

diurn

a l

va

riation, a

nd

r

espo

nse

to

ACTH

stimulation , ar e essentially the sa me in the elde

rl

y and the

yo un

ger

ad ul t [33]. Because t he se baceous glands would not be

aff

ecte

d by a less

than seve

re a

dr

en

ocort

ical insufficiency, it is

unlikely t

hat

the

mod

est a lte ration s in acb'enocortical fun ction

in the aged can accoun t fo r

or

even co

ntribu

te to the

compa

r

at

ively low

sebum

l

eve

ls

of se

nescence,

Studies have suggested a role for t hyroid h

or

mones in the

ma in tenance of se baceo us gland fun ct ion,

Th

yroidectomy in

rats

pro

du

ced significa nt re

du

ct ions in

sebum

secretion, a

nd

thyroxine (T.) administrat ion restored secretion [34]. Seb

um

produ

ct ion levels were found to be lower in p

eop

le with hypo

thyroidism

than

in

norm

a l co

ntrol

s, and treatment

with

L

thyroxine was followed by an increase in sebum produ ct i

on

in

the hypothyroid patients [35]. Alt

hou

gh in elderly men

plasma

total and free T . conce

nt r

at

ion

s are normal, as is the concen

tration of

protein-bound iodine, the metabolic

cl

earance rate

of

T is re

du

ced, pr es

um

ably a reflection

of

a decreased T., pro

duction r

ate,

Also, pla sma tr iiodothyronine T ,) levels are

lower, probably b

eca

use

of dimini

shed p er

iph

eral conve rsion of

T.,

to

Tl'

No

major sex diff

ere

nces in

thyroid abnormalities

have been no te d, a lthough iso lated studies have reported in

men a lessened t h

yrotro

pin

(TSH)

r

espo

nse to

TSH-releasing

hormone administration and low

er

plasma T , level

s,

As to the

relationship between

thes

e thyroid a lte r

at

ions in aging and the

7/26/2019 Age n Sebaceous Gland

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110

POCH

I , S

TR AUSS,

A

ND DOWN

I N G

sebaceous gla

nd

s, it is ent irely possible that the decreased

thyroid fun ction t h

at

occm s with aging has a depressive influ

ence

on

sebaceous lipid synthesis.

Howeve

r, the cha nges de

scr

ibed above are

n

ot

part

ic

ul

ruly ma rked, a

nd

there are con

trad

ictory data conce rning them [36].

I t

is

un l

ike

ly th

at

any

signifi

ca

nt effect is

exerted

since men

are

m

or

e apt to have

d

ecrease

d th

yro

id

ac t

ivi

ty

in

se

nescence a

nd yet they

ma inta in

un

changing seb

um

l

eve

ls

un

t il

at

least the age

of

7U.

SEBACEOUS GLANDS IN T HE AGED

Alt hough, as described in the preceding

sect

ion, t he quantity

of surface Li pids in skin areas where sebaceous gla nds are

nor ma lly ab

und

ant

decreases

with age, P lewig.

and

Kligman

have recently demonstrated by pla nim etric

stu

dy that the

gl

ands

ac tua lly become larger ra th

er

than sma

er

[37]. T hi s

effect

is t he opposite

of

what one migh t

expect

to occm in a

holocrine-secret ing gla

nd

. Actually, Lee had ea rlie r

obse

rved

striki ng hypertro

ph

y and hyperpl

as

ia of the sebaceous glands

in t he foreh

eads of

9

me

n over t he age

of

40 [38]. Ho wever , in

a s ubsequent in

vest

igation, Ka Llapravi t, wh o st udied fewe r sub

jects,

fo

und

th

at

gla nds in age d

me

n we re the

sa

me s ize as t hose

in yo un g

adu

lt

me

n [39].

Tab le

II

I shows data from the study by P lew ig a nd Kligma n

in which t he s ize

of

the se baceous gla

nd

s

in

me

n

in

cr

ease

d wit h

age. I n 3 groups

of

men

of

differe nt ages, ad di tiona l com

pa

r

at

ive

measurements were made of the re l

at

ive volu

me

of skin occu

pi

ed

by the glands in the rem

oved

t i

ssue

spec i

me

n and of the

l

argest

gland

obse

rved in

eac

h

spec

imen. T h

ese

2 indices were

al

so

greater in the elder ly t ha n in t he

yo un

g. T hese investigators

injected t rit iated thym idine a

nd

hi

stid

ine in

trac

uta neo usly in

order

to st udy se baceous gland

ce

llular kin

et

ics. T h

ey

obse rved

reduced cell tmn

over

in the aged gla

nd

s a nd slowe d m ovemen t

of

t he radiolabeled sebaceous ce lls. P r

es

uma bly, t he large size

of

the gla nds w

as

the resul t

of

prolonged ce ll tr ansit t

im

e, in

t he face of continu ed sebaceous lipid synth

es

is. Th is assum

pt

ion

would be consistent wi th the obse rv

at

ions, desc

rib

ed a bove, of

no m

ea

n decrease in surf

ace

lipids in men un der

70

yr

of

age.

However,

the authors, without presenting sp

ec

ific

informat

ion,

me ntion that the se baceous gla

nd

s of elde rly women are simi

lar ly enlarged,

eve

n though se

bum

l

eve

ls are su

bsta

nt ially lower

in

p o s t m ~

women.

In

women,

Lee

did n

ot

find the

se baceous glands to be enlarged, as she did in men

[38].

Sebaceous gland hype

rpl

as ia wi th decreased ce ll t

urn

over,

does not rende r

sebaceo

us gla

nd

s un r

es

ponsive

to

a

ndr

oge nic

st imul

at

ion.

St

udi

es

have demonst ra ted the

ca

pac ity of age d

seb

aceous

gLa

nd

s,

in

both men a

nd

women, to

res

po

nd

to

testostero

ne a

dmini

st

ra t

ion [15,40,41]. F luoxym

este

rone

ca

n

also st imulate postmenopausal sebaceous gla

nd

s (Tab le IV).

T

hu

s, despite t he f

mdin

g th

at

histologi

ca

lly t hey become en

lruged in t he el

de

rly, these gla

nd

s are

res

ponsive

to

horm onal

st imul

atio

n, insofa r

as

detection by surf

ace

lipid

measur

emen

ts

is co nce

rn

ed. I t would be of in terest to

kn

ow wh ether such

treat

ment ca n rend

er

the h

ype

rpl

as t

ic gla nd s sm

alle

r by in

cr

eas

ing cell tUjnover.

Whatever the r

easo

ns for th e hyperplas ia a

nd

d

ec

reased

ac tivity

of

aged

sebaceo

us glands, there are no obvious mor-

ph ologi

ca

l abnormaliti

es

of individual sebaceous

ce

lls [37,42].

However, clusters of

undiffere

ntiat ed ce lJs

ca

n ofte n be

see

n

ar ising from the follicular epi the

lium

of seb

aceo

us follicl

es

.

T BLE

I l l

.

Planimet

ric meas

ur

eme

nt of

sebaceous gland size in

facial biopsy specimens from men

Age

No. subj ec ts

M

ean

cross-secLiona l

area

(mm ' )

20-36

15

.2258

47-53 5 .2532

64-74

21 .4003

Ad

apted from Plewig and Kli gman, Invest Derm alol 70:314 1978

[37].

Vol. 73, N O.1

Although undifferentiated

ce

l s do not r e

pr

ese

n t a spec ific

senescent cha nge, t h

ey

do occ

ur

in great er nu mbe rs tha n llt

yo

un

ge r individ

ua

ls [42]. Unl ike no

rm

al se baceous ce lls, w h

ich

rue strongly r

eact

ive for succ inic dehydrogenase, th

ese

un dif.

fe rentiating cell

rests

show li ttle

reactiv

ity fOl this enzym e.

BREAST C

AN

CER IN

PO S

TME N

OPAUSAL

WOME N

In

a prev ious ar ticle, we reporte d th

at

sebum production,

levels in p

os t

menopa u

sa

l women with breast

ca

ncer were s i

g.

nifi

ca

ntly higher than in age-m

atc

hed controls [43]. Su

bs

e

quent ly, 2 other groups reached the sa me conclusion after

similru

st ud

y

[44,45].

Because pl

as

ma testosterone a nd de h

y_

d

roep

ia

ndros

terone sul

fate

l

eve

ls a re not high

er

in

br

east cancer

patien ts [45,46] nor do such patients become virilized or show

differences in

testoste

rone metabolism as compa red to normal

w

ome

n [

47

] , t

hi

s greate r

sebaceo

us gla

nd

ac tivi

ty

h

as

no ready

expla n

at

ion. Goolam ali and Shu st er suggested the possibility

th

at

a

sebotro

pic f

acto

r mi gh t be pr

ese

n t in pat ien ts with cancel

and migh t be ma

mm at

ropic

as

we ll , for b

ot

h maligna nt

and

beni gn breast di

sease

[48].

Howeve

r , since om origina l report of se bum produ ct ion lev el

in

22

br

east ca

nce r p

at

ients, we h

ave

st udi ed a n addi tional 50

patients, all postmenopausal wit h no previous e

nd

ocrin e surgi.

ca

l in

te

r

ve

ntions or hor

mo

na l t herapy for t heir di

sease

,

and

have com

pared

th

eir

se

bum

l

eve

ls with t h

ose

of a n age- mat ch ed

no

rm

al gro

up

of

51

women. In

eac

h perso n, se bum produ ct ion,

tests were per fo r

me

d on 3 separate

occas

ions. Tab le V shows

the r

es

ul

ts of

o

ur

ini tial

stud

y,

res

ul ts from s

ub

se qu ent reports

by other investi

gato

rs, and our curr ent data . Originally we h ad

fo

und

the mean se bum

pro

du ct ion level for breast

ca

n

cer

pa.

t ien

ts

to be more t han double th

at

of the control gro

up

,

bu

t

We

s

ub

se qu en tly found the difference to be only 25

%

a nd no t

statisti

ca

lly s ignifi

ca

nt (p

>

.1. One might postulate th

at

th er

was a s

ub

gro

up

of

br

east

ca

n

cer

p

at

ien ts wh o fa

il

ed to e

xhi bi

t

the l

owere

d se

bum

levels of aging women, but this

ph

en

omenon

was not characteristic for the gro

up

as a whol

e.

PHYSIOLOGICAL SIGNI FICAN CE OF

SE B

ACEOUS

G

LAND

IN

VOLUT ION

Th e red u

ct

ion in se b

aceo

us gla

nd

ac t

ivity th

at

normally

occurs wit h aging rai

ses

the ques tion

of

wheth

er

SLi ch an invo_

T

BLE IV. E

ff

ect of fl

uoxy

mesterone

on

sebum p r

od

uct ion i

n eight

postmenopausal wom.en

Dose

Sebum pro ci uc lio

l

(mg / l0 cm ' or

hr)

10

mg/ day

Mea.

n

20

mg

/ day

ean

Ages 52 to 67.

0.81

1.26

1.61

1.

23

1.20

1.

34

1.53

1.78

2.38

1.

65

IcaLmen l

1.83

1.62

1.77

1.74

1.47

2.35

l.

89

2.17

2.72

2. 12

T BLE V. Sh

in.

su

rface lipid m

easur

ements in postmenopausal

wome

n

with breast cancer

reast c

n

e l

Kra

nt et al [

43

] 2.11 (22)

Burton et

aJ

[44] I l 0 (20)

W

ang

et

al

[

45

] 0.37 (1

9)

C

urr

ent study 1.29 (72)

Milligrams per 10 cm

2

of skin per 3 hr.

Numbers of subj ects me in pa rentheses.

Normal

s

1.02 (31)

0.76 (20)

0.

24

1

9

0.96 (51)

P value