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THE JOURNAL OF INVESTIGATIVE DERMATOLOGY, 73:108-111,1979 Vol. 73, NO.1
Copyright © 1979 by The Williams & Wilkins Co. 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- comprising cross-sectional analyses in children before and after
ences in their activity as determined by quantitative and the age of 10, showed no increase in sebum secretion until the
qualitative examination of sebum. Sebaceous secretion mid teens, except in menarchal girls, in whom the increase was
is low in children and begins to increase in mid- to late evident somewhat earlier [5]. However, sebum production tests
childhood under the influence of androgens. This rise we performed twice yearly in each of 9 boys and 6 girls for a 3-
continues until the late teens, after which no further yr period showed an earlier increase in sebum production.
significant change takes place until late in life. Figure 1 illustrates our results. A gradual increment in the
In elderly men, sebum levels remain essentially un- amount of sebum secreted occurred; this increment became
changed from those of younger adults until the age of somewhat more abrupt at age 13. No obvious sex difference was
80. In women, sebaceous secretion decreases gradually apparent, either in the quantity of sebum produced at any given
after menopause and shows no significant change after age or in the slope of the line representing sebum secretion.
the 7th decade. The most likely explanation for the de- In actuality, one can observe an even earlier increase in
crease in sebaceous gland secretion with age in both sebaceous gland activity, before the age of 9, by determining
men and women is a concomitant decrease in the endog- the relative composition of skin surface lipids, which are mix-
enous prod.uction of androgens. tures of sebaceous and epidermal lipids [6]. As sebum secretion
Although surface lipid levels fall with age, paradoxi- begins to increase in late childhood, the amount of wax esters,
cally the sebaceous' glands become larger, rather than which are of sebaceous origin, increases relative to the amounts
smaller, as a result of decreased cellular turnover. None- of cholesterol and cholesterol esters, which are epidermal lipids.
theless, as the higher surface lipid levels after adminis- One can show that the wax esters/[ cholesterol+cholesterol
tration of fluoxymesterone (a synthetic testosterone de- esters] ratio increases at approximately 7 or 8 yr of age and
rivative) indicate, the glands have the capacity to re- these lipids approach an "adult" composition by age 10 or 11
spond to androgens. [7,8].
Published results of studies based on examinations of individ-
uals of different ages suggest that full sebaceous gland matu-
Sebaceous gland activity decreases with advancing age [ll ration is not attained until either late in the 2nd decade or early
The principal cause for this attrition appears to be diminished in the 3rd decade [4,5,9,10]. Figure 2 shows data obtained in a
hormonal stimulation, a reversal of the increase in glandular 13-yr longitudinal study of sebum secretion in 2 children, a boy
activity that occurs at puberty through augmented elaboration and a girl. Sebum production was measured in each of the
of androgenic steroids. This review is concerned with studies children 4 times yearly. Secretion clearly increased at age 12 or
on sebaceous gland activity in the aged and the correlation of 13, continued to increase gradually and steadily until age 17 or
these findings with hormonal alterations that occur in late 18, and then appeared to enter a stable phase. Our lack of
middle age and senescence. Data are also presented on the evidence for an earlier sebum increase in the girl was in contrast
developmental changes occurring from the time the glands to another report [5] which indicated greater production in 11-
begin to mature to the time they reach their adult state. to 15-yr-old girls, especially menarchal ones.
METHODS SEBUM STUDIES IN THE AGED
In our laboratories, sebaceous gland activity is measured by a method Once maturity has been achieved, little change in sebaceous
[2] that involves the absorption of surface lipids from a defined area of gland activity takes place until middle age and thereafter. Table
the forehead onto absorbent papers for a period of 3 hr. The lipids
collected are extracted by ether and measured gravimetrically. The I shows sebum production values in women and men 40 yr or
determination of individuai lipid class components of forehead surface older. Average sebum production levels in the women fell by
lipids is made by thin-layer chromatographic separation and photoden- approximately 40% in the 6th decade, declined additionally in
sitometric quantification [3]. the 7th decade, and remained constant thereafter. In the men,
no change was observed until the 8th decade. At any age range
SEBACEOUS GLAND DEVELOPMENT examined, mean sebum values in the men exceeded those in
Human sebaceous glands develop during fetal life between the women. This finding of a drop in surface sebum levels with
weeks 13 and 15 of gestation; they attain fair size by the time of advancing age and of a greater decrease in women is in general
birth and then mostly shrink to comparatively small structures agreement with reports of other studies [5,10-15]' Reduced
during childhood [4]. With the onset of puberty and stimulation sebaceous gland activity, as evidenced by lower surface lipid
by androgens, there is glandular hyperplasia and an increase in levels, has also been demonstrated in vitro by diminished
the synthesis and secretion of sebum. Studies by Cotterill et al formation of squalene, and to a lesser extent of wax esters, from
glucose in skin biopsy samples from the backs of elderly men
[16]. .
Reprint requests to: Peter E. Pochi, M.D., Department of Derma- Study of the forehead surface lipid composition in 15 children,
tology, University Hospital, 75 E. Newton Street, Boston, Mass. 02118. 18 young adult women, and 10 postmenopausal women revealed
This work was supported by U.S. Public Health Service grant IROI- wax esters/[ cholesterol+cholesterol esters] ratios that were low
HD11632 (National Institute of Child Health and Development). in the children, high in the young adults, and low in the aged
Drs. Strauss and Downing are currently at the Department of
Dermatology, University of Iowa Hospitals, Iowa City, Iowa. women (Table II). These changes reflect the differences in
Abbreviations: sebaceous gland activity occurring at these various times of life.
T, = thyroxine The most probable explanation for the decrease in sebaceous
T" = triiodothyronine gland synthesis and secretion in the aged is a concomitant
TSH = thyroid-stimulating hormone (thyrotropin) . decrease in the production of androgens. In men, testosterone

108
July 1979 SEBACEOUS GLANDS IN THE AGED 109
1 .5 TABLE II. Comparison at different oges of wax esters/
[cholesterol+clwlestero l esters! ratios in forehead surface lipids
No. s ubjects Ratio
~ Children 15 0.35
:J
o
.r::
Young ad ult 18 7.47
M women
..... 1.0
Postmenopausal 10 1.46
E
u women
cr
fJJ
o
~

.....
"0
'is. In women, androgen sources for sebaceous gland stimulation
::;
Ol 0 .5 I- 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 postmen-
9 10 11 12 13
opausal women, plasma testostero ne levels fall after bilateral
AGE (years) oophorectomy [21] a nd are lower in postmenopausal oophorec-
FIG 1. Sebum production in 15 children tested tw ice yea rly over a
tomized women than in no rmal contro ls [22]. Moreover, t h e
3-yr period. Height of each column represents the mean sebum value concentration of testosterone in t he ovarian vein exceeds t hat
of the results obtained at the age when tested. 0 = 6 girls; ~ = 9 boys. 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
3 .5
17-ketosteroid excretion a nd plasma concentrations of dehy-
droepia ncb'osterone (the principal a dl'enal a ndl'ogen) [25-27].
3 .0 I, Values for these acb'enal a ndl'ogens ar e greater in men tha n in
I ,
:;'" ---- - Mal e
I
I \
,
women, a nd t his differential persists un til a very late age, after
0
:I:
2 .5
- - Female / \ __ _- - ' , which they closely approach one another [25,28,29].
M I ...
"- I Alt hough it is proba ble t hat t he diminished sebaceous gla nd
E / ? - -' secretory activity occurring in the aged can largely be explained
u 2 .0
a by concomitant changes in androgen levels, the possible role of
fJJ
0
~
I
I
" such other hormones as glucocorticoids a nd t hyr oid hormones,
"-
"0
'0.
::;
Ol
1 .5

I
/
I

" (me na rche )


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 activ-
~
1 .0 /
I ity were to occur with aging, t his defect might lead to a blunted
-' sebaceous gland response to a ndrogens, Studies have shown a
0 .5
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
7 8 9 10 11 12 13 14 15 16 17 18 19 2 0 21 22
metabolites [32], but these cha nges are not marked a nd are the
same for both sexes [33]. Moreover, other indicators of adre-
AGE nocortical function, such as plasma cor tisol levels, urinar y free
2. Longi tudinal study of sebum production
FIG 111 the skin of 2 cor tisol excretion, diurna l variation, and response to ACTH
normal human beings. - - - = male; - - = female. 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
TABLE I. Sebum p roduction values in normal men and women 40 yr unlikely t hat t he modest a lterations in acb'enocortical function
of age and older" in th e aged can accoun t for or even contribu te to the compar-
Women Me n atively low sebum levels of senescence,
Age
No. M ean Range No. Mean Range Studies have suggested a role for t hyroid hormones in t he
ma intenance of sebaceous gland fun ction, Thyr oidectomy in
40-49 3.1 1.86 0.12-4.80 50 2.39 0.54-5.14
21 1.05-4.36 rats produced significant reductions in sebum secretion, a nd
50- 59 1.08 0.07-2.38 14 2.43
60- 69 18 0.88 0.22-1.62 14 2.42 0.83-4.95 thyroxine (T.) administration restored secretion [34]. Sebum
70-79 12 0.85 0.33-2.19 13 1.69 0.63-3.23 production levels were found to be lower in people with hypo-
thyroidism than in norma l controls, a nd treatment with L-
" Milligrams of lipid per 10 cm' of skin per 3 hI". thyroxine was followed by an increase in sebum production in
t he hypothyr oid patients [35]. Alt hough in eld erly men plasma
blood levels gradually decline after the 6th decade but do not total a nd free T . concentrations are normal, as is the concen-
fall significantly until a pproximately the age of 70 [1 7-20]. tration of protein-bound iodine, th e metabolic clearance rate of
These hormone data correla te well with t he findin g of no T " is reduced, presuma bly a reflection of a decreased T., pro-
decline in sebum production levels until after the age of 70, On duction rate, Also, plasma triiodothyronine (T,) levels are
t he other ha nd, studies have indicated t hat the fraction of fre e lower, probably because of diminished peripheral conve rsion of
testosterone, the presumed form in which testosterone enters T., to Tl' No major sex differences in thyroid abnormalities
t he target cell, decreases at an earlier age, usually between 50 have been no ted, a lthough isolated studies ha ve reported in
a nd 60 yr [18- 20]. That sebaceous gland activity does not men a lessened t hyrotro pin (TSH) response to TSH-releasing
decrease until a decade or 2 late r attests to the marked sensi- hormone administration a nd lower plasma T , levels, As to t he
tivi ty of t he gland to e ndogenous a ndrogen stimulation, relationship between these t hyroid a lte rations in aging a nd t he
110 POCHI , STRAUSS, AND DOWN I N G Vo l. 73, N O.1
sebaceous gla nds, it is entirely possible t hat th e decreased Alt hough undiffer entiated celJs do not r epresen t a specific
t h yr oid function t hat occm s wit h aging has a depressive influ - senescent cha nge, t hey do occur in greater numbers t h a n llt
ence on sebaceous li pid synthesis. Howeve r, th e cha nges de- yo unger individ uals [42]. Unl ike norma l sebaceo us cells, w hich
scribed above are not particul ru·ly ma rked, a nd there a re con- ru·e strongly reactive for succinic dehydrogenase, these undif.
tradictory data concerning t he m [36]. It is unlikely t hat any ferentiating cell rests show little reactivity fOl· t his enzym e.
significant effect is exerted since men are more a pt to have
decreased t hyroid activity in senescence a nd yet they maintain BREAST CANCER IN POSTME N OPAUSAL WOM E N
unch anging sebum levels un til at least th e age of 7U. In a previous ar ticle, we reported t hat sebum produ ction,
levels in postmenopa usal wome n with breast cancer were s ig.
SEBACEOUS GLANDS IN T HE AGED
nificantly highe r t han in age-matc hed cont rols [43]. S u bs e •
Alt hough, as described in t he precedin g section, t he qua ntity q uently, 2 other groups reached t he sam e conclusion after
of surface Li pids in skin areas where sebaceous gla nds ar e similru· study [44,45]. Because plas ma testosterone a nd deh y_
norma lly ab undant decreases wit h age, P lewig. and K ligman droepia ndrosterone sulfate levels a re not higher in breast can cer
have recently demonstrated by pla nim etric study t hat t he patients [45,46] nor do such patients become virilized or s h ow
glands actua lly become larger rath er th a n smaJJ er [37]. T his diffe rences in testosteron e m etabolism as compared to normal
effect is t he opposite of wh at one migh t expect to occm in a women [47], t his greater sebaceous gland activity has no ready
holocrine-secreting gland . Actuall y, Lee ha d earlie r obser ved expla nation. Goolamali a nd S huster suggested t he possibility
striki ng hypertrophy a nd hyperplasia of t he sebaceous gla nds that a sebotropic factor migh t be presen t in patien ts wit h cancel'
in t he foreh eads of 9 me n over t he age of 40 [38]. However , in a nd migh t be ma mmatr opic as well , for both maligna nt and
a su bsequent investigation, KaLlapra vi t, who studied fewer su b- be nign breast disease [48].
jects, fo und that gla nds in aged me n we re t he same s ize as t hose However , since om origina l repo rt of se bum production level
in yo ung adult men [39]. in 22 breast cance r patients, we have studied a n a ddi tiona l 50
Table III sh ows data fro m t he study by P lew ig a nd Kli gm a n patients, all postme nopa usal wit h no previous endocrine s urgi.
in which t he size of t he sebaceous gla nds in me n increased wit h cal inte rventions or hormo na l t her apy for t heir disease, and
age. I n 3 gro ups of men of differe nt ages, addi tiona l comparative have com pared t heir sebum levels wit h t hose of a n age- match ed
measurements we re ma de of th e relative volu me of skin occu- normal group of 51 wom en. In each person, se bum pro du ction,
pied by the gla nds in th e removed tissue specime n a nd of t he tests were perfo r med on 3 separate occasions. Table V sh ows
largest gla nd observed in each specimen. T hese 2 indices were t he resul ts of our initial study, resul ts from subsequent reports
also greater in t he eld erly t ha n in t he young. T hese investigators by other investigators, a nd our current data. Originally we h ad
injected t ri tiated thym idine and histid ine in trac uta neous ly in fo und t he mean sebum produ ction level for breast cancer pa.
order to study sebaceo us gla nd cellular kinetics. T hey observed tients to be mo re t ha n double t hat of t he cont rol gr oup, but We
red uced cell t mnover in the aged gla nds a nd slowed m ovem en t s ubsequ en tly found th e diffe ren ce to be onl y 25% a nd not
of t he radiola beled sebaceous cells. P resu mably, t he large size statistically s ignificant (p > .1). One might postulate that t h er
of t he gla nds was the resul t of prolonged cell tra nsit time, in was a s ubgroup of breast cancer patie nts wh o fa iled to exhi bit
t he face of continued sebaceous lipid synth esis. This assum ption t he lowered sebum levels of aging women, but t his phenomenon
would be consistent wi t h t he observatio ns, described a bove, of was not cha racteristic for t he group as a whole.
no mean decrease in surface lipids in men under 70 yr of age.
However, t he a uth ors, wit hout presenting specific information, PHYSIOLOGICAL S IGNI FICAN CE OF SEBACEOUS
mentio n t hat t he sebaceo us gla nds of elde rly wom en are simi- GLAND INVOLU T ION
larly enlarged, even though sebum levels are su bstantially lower Th e red uction in sebaceo us gla nd activity t hat normally
in postm~ n opa u sa l wo men. In women, Lee d id not find t he occurs wit h aging ra ises t he question of wheth er SLich a n invo_
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 T ABLE IV . E ffect of fl uoxymesterone on sebum p roduction in. eight
stimulation. Studies have dem onstra ted t he capacity of aged p ostmenop ausal wom.en"
sebaceous gLa nds, in both me n and wome n, to respond to Sebum p ro ci uclio l1 (mg/ l 0 cm' or
testostero ne a dministration [15,40,41]. F lu oxym esterone can ~kin / 3 hr)
Dose
a lso stimulate postm enopa usal sebaceous gla nds (Table IV). ''T'I'caLme n l
T hus, despite t he fmding th at histologically t h ey becom e en-
lru·ged in t he elderly, these gla nds ar e responsive to hormonal 10 mg/day 0.8 1 1.83
1.26 1.62
stimulatio n, insofa r as detection by s urface lipid measurements 1.61 1.77
is concerned. It would be of in ter est to kn ow wh eth er such Mea.n 1.23 1.74
treatment can re nder the hyperplastic gla nds smaller by in- 20 mg/ day 1.20 1.47
creasing cell t Uj·nover. 1.34 2.35
Whatever the reasons for th e hy perplasia a nd decreased 1.53 l.89
activity of aged sebaceous gla nds, t here are no obvious mor- 1.78 2. 17
phological a bnormalities of individual sebaceous cells [37,42]. 2.38 2.72
However, clusters of undifferentiated celJs can often be see n Mean 1. 65 2. 12
arising from th e follicular epi thelium of sebaceous follicles. " Ages 52 to 67.

TABLE Ill. Planimetric m easurement of sebaceous gland size in T AB L E V. Shin. surface lipid measuremen ts in postmenopausal
facial biop sy specimens from men" women. with breast cancer"
Mean cross-secLiona l Breast cancel" l Normals" P value
Age No. s ubjects area (mm' )
Kran t et al [43] 2.11 (22) 1.02 (31) < .01
20-36 15 .2258 Burton et aJ [44] I.l 0 (20) 0.76 (20) < .05
47-53 5 .2532 Wang et al [45] 0.37 ( 19) 0.24 (1 9) < .03
64-74 21 .4003 Current study 1.29 (72) 0.96 (51) > .1
" Adapted from Plewig and Kligman, J Invest Dermalol 70:314, 1978 " Milligra ms per 10 cm 2 of s kin per 3 hr.
[37]. " Numbers of subj ects m·e in pa rent heses.
July 1979 SEBACEOUS GLAN DS IN THE AGED 111
lutional cha nge represents a loss of function t hat compromises 22. Vermeul en A: T he h ormon al activity of t h e postm enopausal ovary .
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