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THE JOURNAL OF INVESTIGATIVE DERMATOLOGY,

73:108-111,1979

Vol. 73, NO.1

Printed ill. U. S .A.

Copyright 1979 by The Williams & Wilkins Co.

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 differences in their activity as determined 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 unchanged 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 decrease in sebaceous gland secretion with age in both
men and women is a concomitant decrease in the endogenous prod.uction of androgens.
Although surface lipid levels fall with age, paradoxically the sebaceous' glands become larger, rather than
smaller, as a result of decreased cellular turnover. Nonetheless, as the higher surface lipid levels after administration of fluoxymesterone (a synthetic testosterone derivative) indicate, the glands have the capacity to respond to androgens.
Sebaceous gland activity decreases with advancing age [ll
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 photodensitometric 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 Dermatology, University Hospital, 75 E. Newton Street, Boston, Mass. 02118.
This work was supported by U.S. Public Health Service grant IROIHD11632 (National Institute of Child Health and Development).
Drs. Strauss and Downing are currently at 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 3yr 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 mixtures 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 11
[7,8].
Published results of studies based on examinations of individuals of different ages suggest that full sebaceous gland maturation 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 boy
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 11to 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 yr 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 men,
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 aged
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 concomitant
decrease in the production of androgens. In men, testosterone

July 1979

SEBACEOUS GLANDS IN THE AGED

1 .5

TABLE II. Comparison at different oges of wax esters/


[cholesterol+clwlestero l esters! ratios in forehead surface lipids

Children
Young ad ult
women
Postmenopausal
women

:J

.r::
M

.....

109

1.0

cr

No. s ubjects

Ratio

15
18

0.35
7.47

10

1.46

fJJ

o
.....
~

"0

'is.
::;
0 .5 I-

Ol

10

11

12

13

AGE (years)
FIG 1. Sebum production in 15 children tested tw ice yea rly over a
3-yr period. Height of each column represents the mean sebum value
of the results obtained at the age when tested. 0 = 6 girls; ~ = 9 boys.

3 .5

3 .0

:;'"

---- -

:I:

- - Female

2 .5

Mal e

\ __ _- - ' ,

...

E
u

/ ? - -'

2 .0

fJJ
0

I
I

""0
'0.
::;
Ol

"-

I,

1 .5

/
I

"

"
(me na rche )

/
I

1 .0

-'
0 .5

10 11 12 13 14 15

16 17 18 19 2 0 21 22

AGE

2. Longi tudinal study of sebum production


normal human beings. - - - = male; - - = female.
FIG

TABLE

111

the skin of 2

I. Sebum p roduction values in normal men and women 40 yr


of age and older"
Women

Me n

Age

No.

M ean

40-49
3.1
1.86
21
1.08
50- 59
60- 69
18
0.88
12
0.85
70-79
" Milligrams of lipid per

Range

0.12-4.80
0.07-2.38
0.22-1.62
0.33-2.19
10 cm' of skin

No.

Mean

2.39
2.43
2.42
1.69
13
per 3 hI".
50
14
14

Range

0.54-5.14
1.05-4.36
0.83-4.95
0.63-3.23

blood levels gradually decline after the 6th decade but do not
fall significantly until a pproximately the age of 70 [1 7-20].
These hormone data correla te well with t he findin g of no
decline in sebum production levels until after the age of 70, On
t he other ha nd, studies have indicated t hat the fraction of fre e
testosterone, the presumed form in which testosterone enters
t he target cell, decreases at an earlier age, usually between 50
a nd 60 yr [18- 20]. That sebaceous gland activity does not
decrease until a decade or 2 late r attests to the marked sensitivi ty of t he gland to e ndogenous a ndrogen stimulation,

In women, androgen sources for sebaceous gland stimulation


are the ovary and a drenal cor tex. We had assumed previously
that t he postmena pausal decrease in sebum production h ad
been t he resul t of ovaria n involutio n and th at the failure of
many subjects to reach prepubertal sebum levels had been du e
to persistent a drenocor tical androgen secretion [4]. However,
subsequent studies demonstrated t hat postmenopausal ovaries
retain a considerable androgen synt hetic capacity, In postmenopausal women, plasma testostero ne levels fall after bilateral
oophorectomy [21] a nd are lower in postmenopausal oophorectomized women than in no rmal contro ls [22]. Moreover, t h e
concentration of testosterone in t he ovarian vein exceeds t hat
in the peripheral blood [23,24] and increases significantly after
administration of human chorionic gonadotropin [24]. However,
a drenocortical a ndrogen secretion must also decrease in women
(a nd men) with age since t here is a gradual decrease in urinary
17-ketosteroid excretion a nd plasma concentrations of dehydroepia ncb'osterone (the principal a dl'enal a ndl'ogen) [25-27].
Values for these acb'enal a ndl'ogens ar e greater in men tha n in
women, a nd t his differential persists un til a very late age, after
which they closely approach one another [25,28,29].
Alt hough it is proba ble t hat t he diminished sebaceous gla nd
secretory activity occurring in the aged can largely be explained
by concomitant changes in androgen levels, the possible role of
such other hormones as glucocorticoids a nd t hyr oid hormones,
merits consideration, There is evidence t hat human sebaceous
glands req uire cor tisol for t heir optimal response to a ncb'ogenic
stimulation [30]. Thus, if impa ired endogenous corticoid activity were to occur with aging, t his defect might lead to a blunted
sebaceous gland response to a ndrogens, Studies have shown a
decreased cleara nce rate of cortisol in t he aged [31,32] a nd less
urinary excretion of 17-ketogenic steroids [27,33] a nd cortisol
metabolites [32], but these cha nges are not marked a nd are the
same for both sexes [33]. Moreover, other indicators of adrenocortical function, such as plasma cor tisol levels, urinar y free
cor tisol excretion, diurna l variation, and response to ACTH
stimulation, ar e essentially the same in t he elderly and t he
yo unger adul t [33]. Because t he sebaceous gla nds would not be
affected by a less than severe a drenocortical insufficiency, it is
unlikely t hat t he modest a lterations in acb'enocortical function
in th e aged can accoun t for or even contribu te to the comparatively low sebum levels of senescence,
Studies have suggested a role for t hyroid hormones in t he
ma intenance of sebaceous gland fun ction, Thyr oidectomy in
rats produced significant reductions in sebum secretion, a nd
thyroxine (T.) administration restored secretion [34]. Sebum
production levels were found to be lower in people with hypothyroidism than in norma l controls, a nd treatment with Lthyroxine was followed by an increase in sebum production in
t he hypothyr oid patients [35]. Alt hough in eld erly men plasma
total a nd free T . concentrations are normal, as is the concentration of protein-bound iodine, th e metabolic clearance rate of
T " is reduced, presuma bly a reflection of a decreased T., production rate, Also, plasma triiodothyronine (T,) levels are
lower, probably because of diminished peripheral conve rsion of
T., to Tl' No major sex differences in thyroid abnormalities
have been no ted, a lthough isolated studies ha ve reported in
men a lessened t hyrotro pin (TSH) response to TSH-releasing
hormone administration a nd lower plasma T , levels, As to t he
relationship between these t hyroid a lte rations in aging a nd t he

110

Vo l. 73, N O.1

POCHI , STRAUSS, AND DOWN I N G

sebaceous gla nds, it is entirely possible t hat th e decreased


t h yr oid function t hat occm s wit h aging has a depressive influ ence on sebaceous li pid synthesis. Howeve r, th e cha nges described above are not particul ruly ma rked, a nd there a re contradictory data concerning t he m [36]. It is unlikely t hat any
significant effect is exerted since men are more a pt to have
decreased t hyroid activity in senescence a nd yet they maintain
unch anging sebum levels un til at least th e age of 7U.
SEBACEOUS GLANDS IN T HE AGED
Alt hough, as described in t he precedin g section, t he qua ntity
of surface Li pids in skin areas where sebaceous gla nds ar e
norma lly ab undant decreases wit h age, P lewig. and K ligman
have recently demonstrated by pla nim etric study t hat t he
glands actua lly become larger rath er th a n smaJJ er [37]. T his
effect is t he opposite of wh at one migh t expect to occm in a
holocrine-secreting gland . Actuall y, Lee ha d earlie r obser ved
striki ng hypertrophy a nd hyperplasia of t he sebaceous gla nds
in t he foreh eads of 9 me n over t he age of 40 [38]. However , in
a su bsequent investigation, KaLlapra vi t, who studied fewer su bjects, fo und that gla nds in aged me n we re t he same s ize as t hose
in yo ung adult men [39].
Table III sh ows data fro m t he study by P lew ig a nd Kli gm a n
in which t he size of t he sebaceous gla nds in me n increased wit h
age. I n 3 gro ups of men of differe nt ages, addi tiona l comparative
measurements we re ma de of th e relative volu me of skin occupied by the gla nds in th e removed tissue specime n a nd of t he
largest gla nd observed in each specimen. T hese 2 indices were
also greater in t he eld erly t ha n in t he young. T hese investigators
injected t ri tiated thym idine and histid ine in trac uta neous ly in
order to study sebaceo us gla nd cellular kinetics. T hey observed
red uced cell t mnover in the aged gla nds a nd slowed m ovem en t
of t he radiola beled sebaceous cells. P resu mably, t he large size
of t he gla nds was the resul t of prolonged cell tra nsit time, in
t he face of continued sebaceous lipid synth esis. This assum ption
would be consistent wi t h t he observatio ns, described a bove, of
no mean decrease in surface lipids in men under 70 yr of age.
However, t he a uth ors, wit hout presenting specific information,
mentio n t hat t he sebaceo us gla nds of elde rly wom en are similarly enlarged, even though sebum levels are su bstantially lower
in postm~ n opa u sa l wo men. In women, Lee d id not find t he
sebaceous gla nds to be enlarged, as she did in men [38].
Sebaceous gla nd hyperplasia wi t h decr eased cell t urnover,
does not re nde r sebaceous gla nds unrespons ive to a ndrogenic
stimulation. Studies have dem onstra ted t he capacity of aged
sebaceous gLa nds, in both me n and wome n, to respond to
testostero ne a dministration [15,40,41]. F lu oxym esterone can
a lso stimulate postm enopa usal sebaceous gla nds (Table IV).
T hus, despite t he fmding th at histologically t h ey becom e enlruged in t he elderly, these gla nds ar e responsive to hormonal
stimulatio n, insofa r as detection by s urface lipid measurements
is concerned. It would be of in ter est to kn ow wh eth er such
treatment can re nder the hyperplastic gla nds smaller by increasing cell t Ujnover.
Whatever the reasons for th e hy perplasia a nd decreased
activity of aged sebaceous gla nds, t here are no obvious morphological a bnormalities of individual sebaceous cells [37,42].
However, clusters of undifferentiated celJs can often be see n
arising from th e follicular epi thelium of sebaceous follicles.

TABLE

Ill. Planimetric m easurement of sebaceous gland size in


facial biop sy specimens from men"
Age

20-36
47-53
64-74

No. s ubjects

15
5
21

Mean cross-secLiona l
area (mm' )

.2258
.2532
.4003

" Adapted from Plewig and Kligman, J Invest Dermalol 70:314, 1978
[37].

Alt hough undiffer entiated celJs do not r epresen t a specific


senescent cha nge, t hey do occur in greater numbers t h a n llt
yo unger individ uals [42]. Unl ike norma l sebaceo us cells, w hich
rue strongly reactive for succinic dehydrogenase, these undif.
ferentiating cell rests show little reactivity fOl t his enzym e.
BREAST CANCER IN POSTME N OPAUSAL WOM E N
In a previous ar ticle, we reported t hat sebum produ ction,
levels in postmenopa usal wome n with breast cancer were s ig.
nificantly highe r t han in age-matc hed cont rols [43]. S u bs e
q uently, 2 other groups reached t he sam e conclusion after
similru study [44,45]. Because plas ma testosterone a nd deh y_
droepia ndrosterone sulfate levels a re not higher in breast can cer
patients [45,46] nor do such patients become virilized or s h ow
diffe rences in testosteron e m etabolism as compared to normal
women [47], t his greater sebaceous gland activity has no ready
expla nation. Goolamali a nd S huster suggested t he possibility
that a sebotropic factor migh t be presen t in patien ts wit h cancel'
a nd migh t be ma mmatr opic as well , for both maligna nt and
be nign breast disease [48].
However , since om origina l repo rt of se bum production level
in 22 breast cance r patients, we have studied a n a ddi tiona l 50
patients, all postme nopa usal wit h no previous endocrine s urgi.
cal inte rventions or hormo na l t her apy for t heir disease, and
have com pared t heir sebum levels wit h t hose of a n age- match ed
normal group of 51 wom en. In each person, se bum pro du ction,
tests were perfo r med on 3 separate occasions. Table V sh ows
t he resul ts of our initial study, resul ts from subsequent reports
by other investigators, a nd our current data. Originally we h ad
fo und t he mean sebum produ ction level for breast cancer pa.
tients to be mo re t ha n double t hat of t he cont rol gr oup, but We
s ubsequ en tly found th e diffe ren ce to be onl y 25% a nd not
statistically s ignificant (p > .1). One might postulate that t h er
was a s ubgroup of breast cancer patie nts wh o fa iled to exhi bit
t he lowered sebum levels of aging women, but t his phenomenon
was not cha racteristic for t he group as a whole.
PHYSIOLOGICAL S IGNI FICAN CE OF SEBACEOUS
GLAND INVOLU T ION
Th e red uction in sebaceo us gla nd activity t hat normally
occurs wit h aging ra ises t he question of wheth er SLich a n invo_
T ABLE

IV . E ffect of fl uoxymesterone on sebum p roduction in. eight


p ostmenop ausal wom.en"
Dose

Sebum p ro ci uclio l1 (mg/ l 0 cm'


~kin / 3 hr)

or

''T'I'caLme n l

10 mg/day

0.8 1
1.26

Mea.n
20 mg/ day

Mean

1.83
1.62

1.61

1.77

1.23

1.74

1.20

1.47
2.35

1.34
1.53
1.78
2.38
1. 65

l.89

2. 17
2.72
2. 12

" Ages 52 to 67.

T AB L E

V. Shin. surface lipid measuremen ts in postmenopausal


women. with breast cancer"

Kran t et al [43]
Burton et aJ [44]
Wang et al [45]
Current study

Breast cancel" l

Normals"

2.11 (22)
I.l 0 (20)
0.37 ( 19)
1.29 (72)

1.02 (31)

" Milligra ms per 10 cm 2 of s kin per 3 hr.


" Numbers of subj ects me in pa rent heses.

0.76 (20)
0.24 (1 9)
0.96 (51)

P value

< .01
< .05
< .03
> .1

July 1979

SEBACEOUS GLAN DS IN THE AGED

lutional cha nge represents a loss of function t hat compromises


t he integrity a nd natmal defenses of t he skin. Functional attribu tes of sebum include t he m ainte na nce of a protective emollient lipid film, retarda tion of water eva poration, a nd shielding
against bacterial a nd fun gal infections. M ost of t he availa ble
evidence suggests t ha t, al t hough in other ma mmalia n species
sebum coats th e fm (to prevent overwetting and hea t loss) a nd
provides a sexu al attractan t a nd te rri torial marker [49,50], in
huma n beings it provides lit tle or no such protection [49]. Yet,
were sebum to h ave demonstr ated importance in ma n, it might
be difficult to ascribe a ny par ticular aging cha nge seen clinically
to a diminu tion or loss of sebum because of other involutional
skin tissue cha nges occmring at t he sam e time. On t he ot her
ha nd, after t he age of 50, decreased sebaceous gla nd activity in
wom en occurs 10 to 20 yr em'lier t ha n in men; therefore, a ny
possible sex differ ences in skin fun ction, especiall y as related to
dryn ess, sensitiveness, susceptibility to infection, etc., might be
attribu table to decreased sebum . H owever , t here is no clear
evide nce of such a specific sexual predilection.

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