npj | women's heal h Re iew
h ps://doi.o g/10.1038/s44294-024-00050-y
Menopausal shi on women’sheal hand
mic obial niches
Check o upda es
Ma ia R. Nie o 1, Ma ia J. Rus 1, Vic o ia A eal-Quecu y 1, Daniel M. Lubián-López 2,3,4 &
Au ea Simon-So o 1
Menopause ma ks a key miles one in women’s aging, igge ing ho monal, his ological, and
mic obiome changes. This e iew explo es how ho monal shi s du ing menopause al e he
mic obiome’s composi ion, a ec ing o al, in es inal, and u ogeni al communi ies, po en ially leading
o disease. The mic obial me abolism o sex ho mones highligh s he bidi ec ional ela ionship
be ween ho mones and he mic obiome. Unde s anding his in e play is c ucial o de eloping
pe sonalized in e en ions o es o e mic obial balance and imp o e women’s heal h du ing
menopause.
The Uni ed Na ions Gene al Assembly has decla ed he pe iod om
2021–2030 as he Decade o Heal hy Aging1.Women’s biology, including
ho monal and gene ic ac o s, may o e some p o ec ion agains age- ela ed
diseases. Women also end o adop heal hie beha io s, such as seeking
p e en i e heal hca e and main aining s ong social connec ions, which
posi i ely impac hei longe i y2. Howe e , despi e hei longe li espan,
women ace unique heal h challenges as hey age. Socioeconomic ac o s
and cul u al no ms, such as li es yle and nu i ion, also a ec hei heal h
and aging expe iences. The e o e, i is essen ial o add ess gende -specific
heal h needs and p omo e cus omized heal hy aging s a egies o imp o e
he well-being and quali y o li e o aging women.
Menopause is he pe manen cessa ion o spon aneous mens ua ion
o 12 consecu i e mon hs esul ing om he loss o o a ian ollicula
ac i i y which ypically occu s a ound age 50 bu a ies na u ally be ween 40
and 59 yea s. Common symp oms include mucosal d yness, ho flashes,
nigh swea s, weigh changes, sleep and mood dis u bances, and inc eased
isks o ca dio ascula , au oimmune, and bone diso de s3. Addi ionally, o al
heal h is comp omised in menopause by bo h hypoes ogenism and aging o
he o al issues. I should be conside ed ha he influence o aging, in
addi ion o sys emic diseases o medica ions, on he appea ance o o al
al e a ions will inc ease wi h age4. Complica ions a ising om d y mou h
sensa ion, empo omandibula dys unc ion, and psychosoma ic diso de s
a e among he mul iple causes o ea ing diso de s obse ed in some
menopausal women5. Al e na i ely, immunological comp omise esul ing
om aging o es ogen decline may significan ly influence he onse o o al
in ec ions.
The human body is a complex communi y composed o hos cells and
mic oo ganisms ha li e in symbiosis. Body niches (o human niches) a e
defined by he in e ac ions be ween he hos and i s mic obio a, shaped by
en i onmen al condi ions6. Consequen ly, he hos ’sfi ness depends on and
canno be seen sepa a ely om i s mic obio a. Al hough he e a e dis inc
human niches, he hos mus balance all body si es o main ain heal h. The
mic obio a loses balance when homeos asis is dis up ed, also known as
dysbiosis7. The mic obiome plays an impo an ole in a ious aspec s o
heal h. Du ing menopause, ho monal changes can influence he composi-
ion and unc ion o he mic obiome, pa icula ly in egions such as he o al,
gu , agina, and skin. Eme ging e idence sugges s ha ce ain gas o-
in es inal mic oo ganisms can di ec ly me abolize sex ho mones such as
es ogen and p oges e one8. In his na a i e e iew, we in oduce he
concep o menopausal shi , which includes physiological and his ological
changesin hehos ,leading oal e a ionsin hecomposi ionandme a-
bolism o he esiden mic obial communi y due o ho monal changes
du ing he aging o women (Fig. 1). The e o e, explo ing he complex
in e ela ion be ween he mic obiome and menopause e eals p omising
a enues o mi iga e menopausal symp oms and imp o e o e all heal h.
S a egies ha include die modifica ions, p obio ics, and pe sonalized
mic obiome- a ge ed in e en ions o e he po en ial o op imize heal h
ou comes among women’saging.
Biological ansi ions du ing menopause
En i onmen al: physiological changes in menopause
Es ogen, p ima ily in he o ms o es adiol and es one, unde goes sig-
nifican a ia ionsac oss di e en s ages o li e, om pube y o menopause.
Du ing ep oduc i e yea s, es adiol is he mos po en and p e alen o m
o es ogen, exhibi ing cyclical fluc ua ions aligned wi h he mens ual cycle,
peaking a o ula ion. This ho mone plays a c ucial ole in ep oduc i e
unc ions, influencing sys emic heal h, main aining bone densi y, ca dio-
ascula heal h, sexual heal h, mood egula ion, and cogni i e well-being.
1Depa amen o de Es oma ología, Facul ad de Odon ología, Uni e sidad de Se illa, Se illa, Spain. 2Depa men o Obs e ics and Gynecology, Uni e si y Hospi al
o Je ez de la F on e a, Cádiz, Spain. 3Depa men o Obs e ics and Gynecology, Viamed Bahía de Cádiz Hospi al, Cádiz, Spain. 4Depa men o Obs e ics and
Gynecology, Facul y o Medicine, Uni e si y o Cádiz, Cádiz, Spain. e-mail: [email protected]
npj Women's Heal h | (2025) 3:3 1
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Howe e , wi h he onse o menopause, he e is a ma ked shi in es ogen
dynamics. The dec ease in o a ian unc ion esul s in a dec ease in es adiol
p oduc ion, leading o es one becoming he dominan es ogen o m.
Unlike es adiol, es one is syn hesized in adipose issue and se es o
main ain ce ain es ogenic ac i i ies a e cessa ion o o ula ion. Howe e ,
o e all es ogenic ac i i y diminishes du ing pos menopause (a e meno-
pause). Se e al s udies ha e associa ed his decline wi h inc eased isks o
os eopo osis, ca dio ascula disease, and cogni i e impai men s3.This
pe iod eflec s he complex in e play o es ogens h oughou a woman’s
li e, wi h es one p o iding a esidual, bu inadequa e, es ogenic e ec in he
absence o highe es adiol le els. These fluc ua ions in emale ho mone
le els may be esponsible o he physical and psychological symp oms
expe ienced by women du ing he menopausal ansi ion ha comp omise
hei well-being.
O al fluids na u ally con ain ho mones9. In he o al ca i y, sali a yand
gingi al c e icula fluids (GCF) play an impo an ole in main aining
heal h in eg i y10. Sali a and GCF sha e some me aboli es and pa hways bu
also ha e unique composi ions. Sali a y is p ima ily composed o wa e ,
mine als, elec oly es, ho mones, enzymes, immunoglobulins, and
cy okines11. The physiological le el o sali a is undamen al o o al heal h
since i influences a ious ac o s in he o al ca i y, such as p o ec ion
agains ca ies, immunological p ocesses, and diges ion12. Sali a has a highly
ac i e na u al es ogen sec e ed by he o a y, 17β-es adiol, p oges e one,
and es one13,14. The de ec ion o es ogen-β ecep o s in sali a y gland
acina and duc al cells sugges s es ogen deficiency as he e iological agen
o he a ia ions in sali a y sec e ion and ino ganic composi ion obse ed
in menopausal women. The composi ion and flow o sali a can also be
influenced by ce ain medica ions such as an idep essan s, an i-
hype ensi es, o al an isep ics, and cance he apies.
Ho monal deficiency could lead o quan i a i e and quali a i e sali a
a ia ions, al e ing o al homeos asis, which a ec s he o al mic obio a and
leads o bac e ial coloniza ion. Changes in sali a y pH and flow a e in
pos menopausal women di ec ly con ibu e o an inc ease in o al diseases15.
Howe e , he e is a con o e sial ela ionship be ween sali a y pH and age16.
The concen a ion o hyd ogen ions inc eases wi h age in pa ien s, placing
hem in mo e acidic en i onmen s. Sali a y pH in menopausal women has
been epo ed o ha e lowe alues in pos menopausal women compa ed o
p emenopausal women, while o he s ha e ound no significan changes in
sali a y pH be ween di e en g oups16–18. A case-con ol s udy published in
2018 (n= 80) e ealed ha pos menopausal women (n= 40) showed
dec eased sali a y flow and pH compa ed o he con ol g oup (n= 40)19.
Then, ho monal changes du ing menopause can lead o a mo e acidic pH in
women, inc easing he isk o o al issue damage along wi h aging. Howe e ,
o he body si es ha e a pH inc ease ha leads o bac e ial in ec ions.
In con as , he gingi al sulcus con ains se um-de i ed gingi al c e-
icula fluid (GCF)20.Thegingi alfluid con ains es adiol and p oges e one,
and i s fluc ua ion a ec s he gingi al issues21. Es ogen dec eases ke a i-
niza ion, inc eases epi helial glycogen, and a ec s fib oblas p oli e a ion
and p o ein p oduc ion. P oges e one enhances ascula pe meabili y,
educes glycosaminoglycan syn hesis, changes collagen p oduc ion a e and
pa e n, and inhibi s IL6 p oduc ion. Female s e oid ho mones exe a p o-
inflamma o y e ec on he gingi a10,22,23. The e a e pe iods o gum
Fig. 1 | Menopausal shi as hos -mic obial-en i onmen al adap a ion o
women’s aging. Hos : His ological changes ep esen ed in he sali a y gland and
o al mucosa could be ound a o he body si es such as epi helium hinning and
issue a ophy. Ho mone ecep o s can be de ec ed in ho monal/sensi i e issues as
he mucosal lining o he gas oin es inal ac , and he emale u ogeni al sys em.
Mic obial: Changes in mic obiome di e si y (dis ibu ion o mic obial species) and
ichness (numbe o species) modified by in e ac ion wi h hos issues, ho monal
me abolism, and en i onmen al changes du ing menopause. O al bac e ia a e no
es ic ed o mucosal niches bu also inhabi o he o al si es like he gums o ongue.
They a e conside ed pa o he esiden o al mic oo ganism communi y capable o
me abolizing sex s e oid ho mones. The menopause pa adox, cha ac e ized by a
dec ease in mic obial dominance bu an inc ease in ichness obse ed in he aginal
niche, may apply o o he body si es wi hin he mic obiome communi y. Clinically,
changes in mic obial fi ness can con ibu e o heal h p oblems such as in ec ions.
En i onmen al: Physiological changes include a educ ion in sali a y fluid. and a
shi in he p edominan plasma es ogen, om es adiol (p oduced in he o a y) o
es one (o igina ed by a oma iza ion o ad enal and ogens in adipose issue),
accompanied by a ma ked dec ease in p oges e one le els du ing he ansi ion om
menopause. Figu e c ea ed using BioRende .com.
h ps://doi.o g/10.1038/s44294-024-00050-y Re iew
npj Women's Heal h | (2025) 3:3 2
inflamma ion such as gingi i is, which in u n is ela ed o an inc ease in
al e a ion o he mic oana omy and he gingi al and subgingi al bac e ial
popula ion24. Al hough es adiol le els dec ease d as ically du ing meno-
pause, ano he es ogen o m such as es one migh impac he gingi al
issue. As he gingi al en i onmen hos s a esiden mic obial biofilm
communi y and sali a con ains a ansien plank onic mic obio a, bo h o al
en i onmen s can influence hos -mic obial in e ac ions du ing ho monal
fluc ua ions. The e o e, i is essen ial o in es iga e whe he o al fluids
con ain a ious concen a ions o ho mones and o ms accessible o he
mic obio a.
Hos : his ological changes in menopause
O a ian ho mone ecep o s a e ound in he mucosa o he nasopha ynx, he
gas oin es inal ac , and he emale u ogeni al sys em25. The ac ion o sex
ho mones influences he issues o he o al mucosa, gingi a, and sali a y gland
issues26. The ho monal a ia ion ha occu s in menopause p oduces a
asomo o al e a ion ha implies changes in ascula pe meabili y and
inflamma ion media o s. Es ogens and p oges e one egula e he mucosal
ba ie and he immune esponse o he emale ep oduc i e ac , which can
cause aginal symp oms i hei le els a e al e ed. The mos common aginal
symp oms associa ed wi h menopause a e aginal d yness due o es ogen
deficiency and hinning o he aginal epi helium, losing i s de ense
elemen s27,28. Some o he mos common pa hologies a e ul o aginal a ophy,
ecu en u ina y ac in ec ions, bac e ial aginosis, and aginal candidiasis29.
As a esul , bu ning, i ching, and s inging appea in he aginal a ea.
The o al and aginal epi helium show simila i ies a he mic oscopic
le el, ega ding hei ul as uc u e, dis ibu ion o hei ke a in filamen s,
pe meabili y o wa e , and chemical composi ion. This is pa icula ly
no ewo hy as he aginalepi helium unde goes a ious changes du ing and
a e menopause, sugges ing po en ial implica ions o he o al epi helium30.
Fu he mo e, se e al s udies ha e ound no significan di e ences be ween
he numbe o epi helial cell laye s o bo h mucosae. Simila ly, he ke a i-
niza ion pa e ns and he dis ibu ion o lipid lamellae in in e cellula spaces
a e simila . All o his sugges s ha gi en hei mic oscopic simila i ies, he
changes obse ed in he aginal mucosa due o he lack o ho monal s i-
mula ion in pos menopausal women can also a ec he o al epi helium in
hesameway
27,30. I has been sugges ed ha he composi ion o he o al,
aginal and in es inal mic obio a may be egula ed by es ogen le els6.
Consequen ly, a dec ease in sex ho mones has been ound o elici an
inc eased inflamma o y esponse in he hos , po en ially p ecipi a ing
dys egula ion in he equilib ium o he o al mic obio a31. The e o e, his can
esul in a ious gingi al pa hologies, wi h menopausal gingi os oma i is
being pa icula ly p ominen .
Wi hin he o al ca i y, bo h he gingi a and sali a y glands ha bo sex
s e oid ecep o s ha ac as media o s o ho monal e ec s in o al issues25,26.
Sali a y glands, like b eas glands, exp ess he es ogen ecep o alpha
(ERα), while ER be a (ERβ) is ound specifically in he gingi a32.ER-αis
exp essed p edominan ly in he a ge issues o classical s uc u es such as
he mamma y glands and endome ium. In con as , ER-βis exp essed
mainly in issues ha ha e ecen ly been iden ified as a s ess a ge , such as
he o al and colonic epi helium33. Fu he mo e, p oges e one ecep o s (PR)
ha e been ound in sali a y glands and gingi al fib oblas s34–36.Menopausal
women may be mo e suscep ible o changes in sali a y flow since acina and
duc al cells in he sali a y gland ha e ho monal ecep o s, especially he
mino , pa o id, and submandibula glands25. The d as ic d op in sex ho -
mone le els a e menopause, pa icula ly es ogen le els, has nume ous
implica ions o he ne ous, ca dio ascula , heuma ic, endoc ine, gas-
oin es inal, and geni ou ina y ac (Fig. 2). In p emenopausal women, sex
s e oid ho mones demons a e di ec asodila a ion ac ion ia hei ecep-
o s, signaling hei ca dio ascula benefi s. In younge women, es ogens
con ibu e o ca diop o ec ion, a unc ion ha diminishes a e
menopause37. Ano he p e alen disease in menopause is os eopo osis,
al hough i s e iology is complex3.A hiss age,ho monalfluc ua ions and
al e ed calcium me abolism can lead o inc eased le els o bone eso p ion,
making his disease mo e p e alen a e menopause.
O al impac o menopausal shi
Du ing menopause, a se ies o physiological changes occu , mainly due o
he decline o es ogens, a consequence o emale ep oduc i e aging38.This
ma ked hypoes ogenism a ec s he s oma ogna hic sys em and he es o
he sys ems, gene a ing a ious gene al and o al clinical mani es a ions ha
comp omise he well-being o women (Fig. 2). Nume ous s udies ha e
explo ed he associa ion be ween o al condi ions and sys emic mani es a-
ions du ing menopause, e ealing a posi i e co ela ion39.
Pe iodon al disease is a ch onic bac e ial-o igina ing inflamma o y
disease ha des oys he suppo ing den al issues, ul ima ely leading o
oo h loss. I is a mul i ac o ial e iological pa hology caused by he in e -
ac ion o a necessa y bu insu ficien p ima y e iological ac o , a suscep ible
hos , and en i onmen al ac o s ha influence bo h40. Sex ho mones a e
conside ed impo an modi ying ac o s ha can inc ease hos suscep ibili y
o pe iodon al pa hogens and he e o e a ec he p e alence, p og ession,
and se e i y o pe iodon al disease41.Significan fluc ua ion in sex ho mone
Fig. 2 | Physiological and his ological changes in
menopause. Main sys emic changes (le panel) and
o al ( igh panel) diso de s. Figu e c ea ed using
BioRende .com.
h ps://doi.o g/10.1038/s44294-024-00050-y Re iew
npj Women's Heal h | (2025) 3:3 3
le els along wi h cha ac e is ic menopausal os eopo osis has led se e al
s udies o link menopause and pe iodon al disease.
Os eopo osis may be esponsible o helowe densi yo heal eola
c es bone pe uni olume, which would p omo e as e bone loss in
esponse o he eso p ion s imula ion p o ided by pe iodon al in ec ion42.
Based on his hypo hesis, a s udy conduc ed in pos menopausal women did
no co ela e a lowe sys emic mine al densi y wi h a g ea e loss o pe i-
odon al a achmen in esponse o o al in ec ion, al hough i was obse ed
ha he associa ion became significan wi h olde age o he pa ien s43.
Howe e , subsequen s udies ha e epo ed a highe p e alence o pe iod-
on al disease in pos menopausal women han in p emenopausal women and
a simila pe iodon al s a us be ween p emenopausal women and pos -
menopausal women who ecei ed menopause ho mone he apy (MHT)44.
Some ha e e en poin ed o MHT as a p o ec i e ac o o den al pain,
imp o ed den al mobili y, and he dep h o he p obing o he pe iodon al
pocke 45. Recen ly, he p e alence and associa ed ac o s o oo h loss in
pos menopausal women ha e been explo ed. The main con ibu ing ac o s
a e poo o al hygiene and low bone mine al densi y46. Al hough some s udies
sugges a posi i e co ela ion be ween hypoes ogenism-os eopo osis and
g ea e oo h loss, mo e esea ch is needed o define he ela ionship be ween
menopause and pe iodon al disease, conside ing con ounding ac o s asso-
cia ed wi h bo h condi ions, such as ad anced age, educa ion, ch onic dis-
eases, obacco and alcohol consump ion, and especially o al hygiene and die .
Tempo omandibula diso de s (TMD) a e a g oup o musculoskele al
diso de s ha a ec he mas ica o y muscles and he empo omandibula join
(TMJ). The highe incidence o TMD in women han in men and he de ec ion
o es ogen and p oges e one ecep o s in he TMJ disc ha e led o con-
side a ion o he ole o emale sex ho mones in he mul i ac o ial e iology o
his join diso de 47. Some au ho s ha e obse ed a highe p e alence and
se e i y o TMD in pos menopausal women han in p emenopausal women48.
In his ega d, a s udy conduc ed in women wi h TMD and di e en mens ual
cycle s a es concluded ha he deg ee o ch onic pain ela ed o TMD, mas-
ica o y dys unc ion, dep essi e symp oms, and soma iza ion was g ea e when
es ogen le els we e lowe 49. Howe e , o he esea che s e alua ed he p esence
o TMD in pos menopausal women and hei ela ionship wi h pain and he
use o MHT and ound no ela ionship be ween TMD and pos menopause, no
be ween he use o MHT and TMD pain50. These con adic o y esul s equi e
u he s udies o unde s and he e ec s o menopause on TMJ.
Es ogen deficiency could be ela ed o changes in sali a sec e ion in
menopausal women due o al e ed sali a y issues39,51. Hyposali a ion is
ela ed o changes in he o al ca i y, such as loss o b igh ness o he o al
mucosa, d yness o he mucous memb anes, fissu es on he back o he
ongue, angula cheili is, hick sali a, inc eased equency o o al in ec ions,
p esence o ca ies in a ypical places, and inc ease in he size o he main
sali a y glands52. Pos menopausal women commonly expe ience o al
symp oms, including d yness, bu ning sensa ion, mou h pain, as e chan-
ges, and oo h loss, o en accompaniedby di ficul ies swallowing, phona ion,
and hali osis53. D y mou h o xe os omia is he main o al symp om du ing
pe i and pos menopause, wi h mos pa ien s epo ing a dec ease in sali a y
flow54. Sali a y p oges e one le els a e di ec ly co ela ed wi h he sensa ion
o o al d yness in menopause15. Howe e , i emains unclea whe he d y-
ness is only associa ed wi h a ho monal dec ease, as o he ac o s such as
medica ion o aging also influence sali a y a e.
The sensa ion o o al d yness is o en accompanied by bu ning mou h
synd ome (BMS), which is also ela ed o ungal in ec ions such as o al
candidiasis in pos menopause55. Emo ional ins abili y, pa icula ly e iden in
pa ien s wi h BMS cha ac e ized by pain and bu ning o he o al mucosa, is
ela ed o psychological diso de s such as dep ession o anxie y, unde sco ing
he mul i ace ed na u e o menopausal o al heal h conce ns51.Fu he mo e,
he e is an inc ease in acial, den al, and empo omandibula complain s and
ulce a ions56. In gene al, dec eased sali a flow leads o o he symp oms such
as bad o al e ed as e, dysphagia, iscous sali a, o al mucosi is, lichen planus,
s oma i is, and pemphigoid. The e o e, i is impo an o add ess o al dis-
o de s in aging women by c ea ing p e en i e o al ca e p og ams and specific
he apeu ic in e en ions ailo ed o menopause.
Mic obial: mic obiome in menopause
O al mic obiome
I has specific body si es (o human niches) defined as he hos -mic obio a
in e ac ion shaped by en i onmen al condi ions57. O al mic obiomes a e
complex ecosys ems o mic oo ganisms ha li e in he o al ca i y and a e in
so and ha d issues, including ee h. Ho monal changes can influence
in e ac ions be ween his mic obial communi y and he hos 58.Theo al
mic obiome is sensi i e o changes in he o al en i onmen , and ho monal
fluc ua ions can c ea e condi ions ha a o he g ow h o ce ain ypes o
bac e ia o e o he s. De ec ing sys emic changes in ho mone le els in heal h
and disease by analyzing he o al mic obiome could be ele an when
ho mone changes a ec he o al mic obiome. Ho monal fluc ua ions, such
as hose ha occu du ing pube y, mens ua ion, p egnancy, and meno-
pause, can a ec he o al ca i y. Fo example, ho monal changes can a ec
sali a p oduc ion and al e i s composi ion, which can influence he o al
mic obiome59. In menopause, na u ally occu ing al e a ions in ho mone
le els could also impac he esiden mic obial communi y.
Sali a y flow and composi ion ha e a con o e sial link o menopause.
The AMICA p ojec compa ed he o al mic obiome in sali a o 20 pos -
menopausal women wi h he con ol g oup (n= 19 women o ep oduc i e
age). The s udy did no find significan di e ences in he composi ion o he
o al mic obiome in sali a be ween menopausal women and hose wi h a
egula mens ual cycle60. The mos abundan bac e ial gene a we e hose
al eady known o be p edominan in heal hy indi iduals, such as S ep o-
coccus, Neisse ia, Po phy omonas, P e o ella, and Veillonella60.Incon as ,
Teles and cols. iden ified ha he dominan amilies o he s udy popula ion
we e P e o ella and S ep ococcus61. Specifically, P e o ella cop i was sig-
nifican ly highe and Veillonella obe suensis dec eased a e menopause39.
Fu he mo e, women who expe ience se e e hyposali a ion ha e simila
bac e ial p ofiles compa ed o hose wi h no mal sali a y flows. Significan
me aboli e changes we e iden ified in pos menopausal women’s sali a, wi h
es adiol le els posi i ely ela ed o uns imula ed sali a y flow60.Ano he
s udy iden ified di e ences in sali a y composi ion ela ed o hyposali a ion
wi hin aging women, pa icula ly ocusing on he o al mic obiome59.The
findings sugges ha dec eased es adiol le els due o educed sali a y flow
can cause o al p oblems in menopause and al e ce ain o al bac e ia. Fu he
in es iga ion wi h ex ensi e popula ion and longi udinal s udies will eluci-
da e he impac o he menopause ansi ion in sali a y en i onmen s.
Sali a y co isol is a bioma ke used o examine he esponse o human
s ess62. Psychosoma ic head and neck diso de s such as aph hous s oma-
i is, a ypical acial pain, o al lichen planus, BMS, and xe os omia ha e been
associa ed wi h he menopausal s age. In a clinical ial ha included 200
pos menopausal women, sali a co isol le els we e e ealed o be s a is ically
significan , demons a ing highe le els in pos menopausal women wi h
psychosoma ic diso de s62. A ecen me a ansc ip omics unc ional ana-
lysis on he e ec o s ess- ela ed co isol on he o al mic obiome iden ified
ha membe s o he Fusobac e ia phylum become mo e ac i e in he p e-
sence o co isol63. In e es ingly, Lep o ichia good ellowii, p e iously ela ed
o gingi i is, was subs an ially mo e dynamic. In gene al, exposu e o co -
isol in he o al mic obiome can change he ac i i y o he en i e bac e ial
communi y61. Some o hese changes include o e ep esen a ion o he
hos ’s immune esponse agains o al bac e ia and inc ease in p o eolysis,
oligopep ide anspo , i on me abolism, and flagella assembly on he bac-
e ial side. These ac i i ies ha e p e iously been associa ed wi h unc ional
dysbiosis and he p og ession o o al diseases, such as pe iodon al disease63.
This aises he in e es ing possibili y ha o al mic oo ganisms may espond
di ec ly o he p esence o s ess ho mones.
Biofilm-associa ed pe iodon al disease is a common o al disease in
aging and menopausal women. The subgingi al mic obiome o pos -
menopausal women has been co ela ed wi h he p esence and se e i y o
pe iodon al disease. Some o he mos cha ac e is ic pa hogens associa ed
wi h his disease belong o Bac e oides,Tanne ella o sy hia,Po phy omonas
gingi alis,Spi oche es,T eponema den icola,Bac e oidales,and
Fusobac e ium24. The in e ac ions be ween Fi micu es and Bac e oides can
be a good indica o o mic obial habi a in aging pa ien s. A end owa d a
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highe p opo ion o Fi micu es o Bac e oides has been desc ibed in
menopausal women61,64. Specific species su i e wi hin he subgingi al
mic obiome o menopausal women ega dless o he exis ence o se e i y o
pe iodon al disease. In pa icula , hese include Veillonella dispa ,Veillo-
nella pa ula,S ep ococcus o alis,andBifidobac e ium den ium61. S udies
ha e indica ed ha he p esence o B. den ium can inhibi P. gingi alis
p oli e a ion, a no able pa hogen implica ed in pe iodon al disease65.This
obse a ion may p o ide insigh in o why P. gingi alis was de ec ed a
ela i ely low le els in a coho o aging women wi hou pe iodon al disease.
The o al mic obiome changes du ing menopause, wi h specificpa hogens
con ibu ing o pe iodon al disease in aging women. Despi e his, ce ain
species pe sis in he subgingi al mic obiome o menopausal women,
po en ially influencing pe iodon al heal h.
The gingi al c e icula fluid is a pe iodon al exuda e composed o
se um con aining a ious me aboli es ha in e ac wi h he esiden pe i-
odon al mic obio a66. Clinically, inc eased pe iodon al inflamma ion has
been associa ed wi h ho monal dys egula ion si ua ions such as p egnancy
and es ogen-dependen diseases such as endome iosis67. Consequen ly,
many subgingi al o ganisms associa ed wi h pe iodon al disease in olde
women we e compa able o he subgingi al mic obio a obse ed in s udies
o young indi iduals wi h pe iodon al disease. A no able excep ion is he
absence o A. ac inomyce emcomi ans, associa ed wi h agg essi e pe iod-
on i is, which is a e in olde adul s22.Thesefindings sugges complex
dynamics be ween he o al mic obiome and menopause, wi h implica ions
o esea ch and he apy.
Al hough p e ious s udies ocused on bac e ial species, i is essen ial o
ecognize he ole o commensal ungal popula ions in he o al mic obial’s
complexi y. Du ing menopause, he p oli e a ion o ungi inc eases due o
aging and ho monal imbalance, leading o dysbiosis and he p oli e a ion o
oppo unis ic species such as Candida albicans, pa icula ly in he pos -
menopausal s age68. An ibio ics, local o sys emic immunosupp ession as
ch onic use o sys emic o inhaled s e oids, hyposali a ion, diabe es melli-
us, and smoking con ibu e o he de elopmen o candidiasis.
Ch onic candidiasis can cause a bu ning sensa ion in he mou h, a
cha ac e is ic symp om o bu ning mou h synd ome (BMS), sha ing sig-
nifican ac o s such as ch onic use o medica ions and he p esence o
emo able p os heses. Howe e , while C. albicans has been de ec ed in
45.16% o pos menopausal women wi h BMS, bu i s associa ion wi h he
e iology o he synd ome emains inconclusi e51,69. Physiological pa ame e s
such as pH and sali a y flow did no significan ly influence he p esence o
C. albicans, sugges ing a complex in e play o ac o s in i s coloniza ion.
Al hough he dis ibu ion o Candida species a ied be ween samples,
physiological changes du ing menopause could con ibu e o ungal p o-
li e a ion. Thus, menopause does no di ec ly inc ease he isk o o al
candidiasis70. Al hough no associa ion was obse ed be ween sali a y flow
and C. albicans in asion in pos menopausal women, he p e ious li e a u e
sugges s a po en ial link, possibly influenced using p o on pump inhibi o s
ha a ec he o al mic obio a. Recen esea ch has iden ified Candida
glab a a as an oppo unis ic pa hogen esponsible o mucosal and sys emic
in ec ions, o en ound in elde ly, immunosupp essed indi iduals, and
se ings associa ed wi h heal hca e71. Mo e esea ch is needed o elucida e
he in ica e ela ionship be ween sali a y flow, ho monal changes, and
ungal coloniza ion du ing menopause.
The menopause mic obiome beyond he o al niche
Mucosal ecep o s o o a ian ho mones ha e been ound in he b ain, o al
ca i y, nasopha ynx, gas oin es inal ac , and emale u ogeni al sys em22
(Fig.3). This sugges s ha he composi ion o he ne ous sys em, o al,
Fig. 3 | Mic obial-hos in e ac ions influenced by sex s e oid ho mones. Ho -
monal fluc ua ions induce changes in he cha ac e is ics and unc ions o hos issues
and body fluids, al e ing he en i onmen o mic obial communi ies. Menopause
mic obial niches include o al and in es inal as gas oin es inal ac (GIT) and
emale ep oduc i e ac and u ina y si es as u ogeni al sys em (UGS). Me abolism
o sex s e oid ho mones by esiden human mic oo ganisms can influence hei
a ailabili y in he body, po en ially leading o al e a ions in ho monal le els and
impac ing o e all heal h. Figu e c ea ed using BioRende .com.
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in es inal, aginal, and bladde mic obiome can be egula ed sys emically by
sex ho monal le els72. Al hough ma kedly di e en ecosys ems, some bac-
e ial species sensi i e o ho monal changes may be p esen in di e en
issues, such as hose o he o al, in es inal, and geni ou ina y body si es73
(Fig. 3). Fo example, some s ains o Lac obacillus ha e been ound o
colonize he mou h, agina, and ec um simul aneously and may pass om
he in es ine o he agina h ough he pe i oneum74. The ho monal an-
si ion o menopause could mani es di e en hos -mic obio a in e ac ions
a specific body si es.
The in es inal mic obiome. Eme ging e idence sugges s ha he gu
mic obiome could significan ly con ibu e o ho mone- ela ed al e a-
ions obse ed in women’s aging, pa icula ly du ing he ansi ion o
menopause75. Since he gas oin es inal ac is unde s ood om he o al
o he anus, he bac e ial communi ies obse ed in he in es ine may be
ela ed o he o al communi y and ice e sa8. The di e si y o he
mic obial communi y’sα-di e si y, de e mined by he dis ibu ion o
mic obes wi hin a sample, encompasses bo h he coun and he ela i e
abundances o he axa p esen . S udies indica e ha menopause is
associa ed wi h al e a ions in he di e si y o he gas oin es inal
mic obio a due o declining ho mone le els76,77. Howe e , con as ing
findings sugges ha he e a e no disce nible di e ences be ween p e-
and pos menopausal women27,78–80.
The changes su e ed in he in es inal mic obiome h oughou
women’s aging a e ge ing a en ion om esea che s. A longi udinal s udy
ound ha he in es inal mic obiome in pos menopausal women (n= 1027)
was less di e se han in p emenopausal women (n= 295). Fu he mo e,
hey ound ha pos menopausal women had a highe abundance o Bac-
e oides sp. Ga6A1,P e o ella ma shii, Veillonella dispa and Su e ella
wadswo hensis76. Gene a P e o ella and Su e ella ha e p e iously been
associa ed wi h obesi y in o he s udies81. Simila ly, in es inal Bac e oides
can ha e beneficial o ha m ul e ec s depending on he ela ionship wi h
o he mic obiomes and hos ac o s82. Mic oo ganisms ha find he
app op ia e condi ions in he mou h, such as P e o ella,Bac e oides sp,and
Fi micu es, p oduce di e en ypes o communi y a he gas oin es inal
le el. Fu he mo e, a lowe abundance o Esche ichia coli-Shigella spp.,
Oscillibac e sp. KLE1745, Akke mansia muciniphila, Clos idium lac a i-
e men ans, Fi micu es,Abio ophia,Pa abac e oides johnsonii,andVeil-
lonella seminalis75. I emains unclea whe he changes in ho monal le els
du ing he ansi ion o menopause could a ec he balance o he in es inal
mic obio a, po en ially esul ing in dysbiosis.
Sexual dimo phism in he in es inal mic obiome e e s o he di e -
ences be ween men and women in mic obial composi ion and di e si y.
While he e is no sex dispa i y in he in es inal mic obio a be o e pube y, a
no able change occu s a e pube y, cha ac e ized by a gene al educ ion in
mic obial di e si y in men compa ed o women. Specifically, women exhibi
a highe gu mic obiome ichness and a lowe abundance o P e o ella
compa ed o men8,83–85. The in es inal mic obio a o pos menopausal
women exhibi ed a g ea e simila i y o ha o men compa ed o p e-
menopausal women76,78. Howe e , he impac o P e o ellaonhumanheal h
is conflic ing, as i s e ec s a y depending on he specific s ains in ol ed.
The communi y o mic oo ganisms ha eside in he diges i e ac
pe o ms mul iple unc ions, such as me abolism o die a y componen s,
syn hesis o lipopolysaccha ides om G am-nega i e bac e ia (in ol ed in
inflamma ion), and me abolism o endogenous componen s, including
emale ho mones86. A e menopause, an inc eased incidence o au o-
immune diseases has been obse ed87.Ruminococci,o hegenusClos idia,
a e p oduce s o sho -chain a y acids, as hey ha e neu oac i e p ope ies
ha allow communica ion o he b ain-gu axis, being a beneficial
unc ion88–90. A educed abundance o some Ruminococcus species has been
obse ed in pa ien s wi h C ohn’s disease and sys emic Lupus
e y hema osus91,92. Highligh , a lowe abundance o Ruminococcus has been
associa ed wi h pos menopausal women compa ed o p emenopause78,93,94.
Since ca dio ascula disease is one o he leading diseases in aging
women, ecen esea ch e alua ed he ole o he gu mic obiome in
ho mone- ela ed ca dio ascula p o ec ion95. A la ge pos menopausal
coho collec ed s ool samples and se um le els o 15 sex ho mones, finding
es ogen associa ed wi h highe di e si y and abundance o Alis ipes,Col-
linsella,E ysipelo ichia,andClos idia. In e es ingly, hey sugges ed ha he
connec ion be ween es one and ca o id a e y plaque may be influenced by
he gu mic obiome. Howe e , he p esence o HIV in 81% o he women
included in he s udy could po en ially dis up he di ec co ela ion
be ween sex ho mones and he mic obiome. On ano he no e, p oges e one
educes immune sys em ac i i y, leading o inc eased ulne abili y o
pa hogens96. P oges e one le els dec ease concomi an ly wi h es ogen a e
menopause. Plasma p oges e one concen a ion in pos menopausal women
p edic ed ci cula ing p oges e one le els acco ding o he composi ion o
he gu mic obiome78. Es ablishing he specific oleo hesebac e iain he
in es inal mic obiome and hei ela ionship o menopause is challenging
due o he lack o mechanis ic s udies. The e o e, he specific heal h
implica ions o he gu mic obiome in he aging o women a e no well
unde s ood.
U ogeni al mic obiome. The aginal mic obiome unde goes p o ound
changes du ing menopause, a ec ing women’s heal h and suscep ibili y
o a ious in ec ions. Specifically, a he aginal le el, his imbalance can
igge ch onic inflamma ion, which could con ibu e o an ele a ed isk
o ce ain in ec ious diso de s such as a ophic agini is, pel ic agini is,
bac e ial aginosis, geni al candidiasis, sexually ansmi ed in ec ions,
and HIV27. A pe sis en s a e o inflamma ion and associa ed in ec ions
can also inc ease he likelihood o malignan ans o ma ions, hus
inc easing he isk o ca cinogenesis97. This unde sco es he po en ial
implica ions o menopausal ho monal changes on aginal heal h and
associa ed isks.
Recen s udies show ha changes in he ep oduc i e mic obiome
du ing menopause a e linked o highe isk o endome ial cance (EC).
Walsh e al. 98 ound ha he mic obiome becomes mo e di e se in pos -
menopausal women, which may inc ease disease isk98. Specifically, Po -
phy omonas some ae and A opobium aginae we e mo e common in
women wi h EC. Addi ionally, Po phy omonas gingi alis, associa ed wi h
Alzheime ’s and pe iodon al diseases, is closely ela ed o P. some ae sug-
ges ing ha Po phy omonas species may play a ole in disease du ing
menopause.
Mic obiome fi ness e e s o he heal h and esilience o he mic obial
communi y in specific en i onmen s like he gu , o o al ca i y. A heal hy
mic obiome is di e se, and composed o beneficial mic oo ganisms ha
suppo hos heal h, while an imbalanced mic obiome may lead o disease.
In he heal hy aginal mic obiome, Lac obacillus species a e ypically he
p edominan bac e ia p oducing lac ic acid and c ea ing an acidic en i -
onmen ha helps p e en he o e g ow h o ha m ul bac e ia. This dom-
inance is impo an o main aining aginal heal h and p e en ing
in ec ions.
Menopause pa adox con as ing ends obse ed in he aginal
mic obiome be ween p emenopausal and pos menopausal women. The
menopause pa adox desc ibes a phenomenon in menopausal women
cha ac e ized by a dec ease in Lac obacillus dominance and an inc ease in
mic obial ichness in he aginal mic obiome. As a esul , he aginal
mic obiome in pos menopausal women may become mo e di e se,
adap ing o a b oade spec um o mic obial species wi hin he niche. Hos
and en i onmen al changes con ibu e o he pa adoxical ela ionship
be ween dominance and ichness in menopausal women, including changes
in ho mone le els, aginal pH, and hos immune esponse. F om a clinical
pe spec i e, his pa adox can lead o heal h issues like in ec ions due o
changesinmic obialfi ness, emphasizing he impo ance o add essing
hese mic obiome shi s in menopausal women’sheal hca e
99.
Fi s , ho monal changes associa ed wi h menopause can al e he
aginal en i onmen , a ec ing mic obial communi ies. The decline in
es ogen le els du ing menopause leads o changes in aginal pH and
mois u e le els, c ea ing an en i onmen ha con ibu es less o he g ow h
o ce ain mic obial species, pa icula ly Lac obacillus, which a e dominan
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in p emenopausal women. The aginal mic obiome is classified in o fi e
ypes o communi y s a e (CST), de e mined by he p esence and abun-
dance o Lac obacillus species. CST I is cha ac e ized by he p edominance
o L. c ispa us, while CST II, III, and V a e domina ed by L. gasse i,L. ine s,
and L. jensenii, espec i ely. In con as , CST IV lacks Lac obacillus and
includes anae obic mic obes such as P e o ella and Ga dne ella
Ga dne ella100,101.
Pos menopausal women expe ience educed Lac obacillus le els,
inc easing mic obial di e si y102. Howe e , his may lead o enhanced sus-
cep ibili y o anae obic bac e ial coloniza ion, associa ed wi h in ec ions.
When he bac e ial di e si y inc eases, he de ec ed species include P e-
o ella, Po phy omonas, Pep oniphilus, Anae ococcus, Pep os eo ococcus,
Dialis e , A opobium, Ga dne ella, Megasphe a,andBacillus,somea e
associa ed wi h ce ain aginal in ec ions, such as bac e ial aginosis (BV)28.
Clinical esea ch demons a es ha he anae obic o e g ow h cha ac e is ic
o BV is ela ed o he mic obio a o pos menopausal women compa ed o
p emenopausal women. Fu he mo e, a co ela ion has been desc ibed
be ween a aginal flo a domina ed by non-Lac obacillus and aginal
d yness97. Women wi h mo e se e e signs and symp oms o aginal d yness,
dyspa eunia, and aginal pain end o ha e a g ea e di e si y o he aginal
mic obio a ha is no p edominan ly Lac obacillus.The P e o ella and
Po phy omonas species a e cons i uen s o he emale geni al ac and he
o al ca i y, con ibu ing o polymic obial in ec ions such as bac e ial agi-
nosis and o al pe iodon i is103.
Fu he mo e, di e ences in immune unc ion and aginal heal h
be ween p e- and pos menopausal women can also con ibu e o he
pa adox o di e si y and ichness. Changes in immune esponse and aginal
epi helial in eg i y can influence mic obial coloniza ion pa e ns and
communi y s uc u e102.Lac obacillus species p o ec a woman agains
in ading pa hogens by lac ic acid e men a ion, p omo ing aginal and
bladde heal h. The mos significan di e ence be ween p e- and pos -
menopause is he dec ease in Lac obacillus le els. The main me abolic
pa hways o Lac obacillus a e lac ic acid and glycogen. Lac obacillus con-
ibu es o mic obial equilib ium by e adica ing dysbio ic mic oo ganisms
and a ious pa hogens h ough lac ic acid, a p ima y an ibac e ial agen 38.
Lac obacillus p ima ily p oduces lac ic acid, which dec eases ma kedly in
pos menopausal aginal fluid wi h highe pH compa ed o p emenopausal
le els. The lac ic acid analysis e ealed ha he p emenopausal g oup
exhibi ed a lac ic acid coun o 98%, ep esen ing a subs an ial po ion o he
o al. In con as , in he pos menopausal g oup, he lac ic acid concen a ion
dec eased ma kedly o 94.2%102. Highe le els o es ogens p omo e he
accumula ion o glycogen in he aginal epi helium, p omo ing he dom-
inance o Lac obacillus104. Inc eased ee glycogen le els p omo e a hicke
s a ified squamous epi helium and a p o ec i e mucus laye , which is also
co ela ed wi h highe Lac obacillus le els105. Du ing p emenopause, ee
glycogen le els in he aginal mucosa a e significan ly highe han du ing
pos menopause106. In con as , es ogen le els d op d as ically, so he
aginal mic obio a and epi helium could be a ec ed. Pos menopausal
women ha e lowe Lac obacillus le els, pe haps due o a dec ease in
accessible es ogen-dependen glycogen. Fu he mo e, in women wi h
aginal a ophy, he bac e ial mic obio a is absen 28.
The geni ou ina y sys em is closely ela ed o he agina. The aginal
mic obiome in e ac s wi h o he mic obial communi ies in he u ina y and
gas oin es inal sys ems. Vaginal Lac obacillus maybep o ec i ein he
u ina y ac 74. Fu he mo e, he u ina y ac may ac as a ese oi o
aginal Lac obacillus and may help ecolonize a e dysbiosis, p oduced by
some me abolic change o pa hology associa ed wi h menopause. Among he
Lac obacillus species, L. jensenii, also commonly ound in he u e h a, along
wi h L. ine s and L. c ispa us, is he mos equen ly isola ed in he agina107.
The co ela ion be ween Lac obacillus abundance in he agina and i s p e-
sence in he u e h a is s iking. Consequen ly, p omo ing Lac obacillus
coloniza ion in he agina can posi i ely impac i s p esence in he u ina y
sys em, hus playing a i al ole in women’s heal h, especially pos menopause.
U ogeni al complica ions a e expe ienced by one- hi d o women 50
yea s o olde . The u ina y sys em may also be a ec ed due o mucosal
d yness. Geni ou ina y symp oms such as dyspa eunia, dysu ia, and
ecu en u ina y ac in ec ions (UTI) can appea 101.The eisapa hology
called geni ou ina y synd ome o menopause (GSM) ha a ec s app oxi-
ma ely 50% o menopausal women, again a ec ing he sexual and unc ional
heal h o women101. Menopause induces changes in he aginal mic obiome
ha esul in aginal symp oms28. A s udy in 2021 iden ified P e o ella and
Po phy omonas, which a e classical pe iodon al pa hogens, as mic o-
o ganisms associa ed wi h UTIs ea ed wi h an ibio ic he apy101. A c oss-
sec ional s udy in 2013 (n= 87) demons a ed ha mild o mode a e ul-
o aginal a ophy shows a g ea e di e si y in he mic obio a in he absence
o Lac obacillus han in women wi hou ul o aginal a ophy who showed a
mic obio a domina ed by Lac obacillus c ispa us72.Thus, hecomplexi yo
aginal mic obiome dynamics and he need o a mul i ace ed app oach o
elucida e he unde lying mechanisms. Fu u e esea ch should employ
longi udinal s udies and ad anced omics echnologies o un a el he in i-
ca e in e ac ions be ween hos physiology, mic obial composi ion, and
en i onmen al ac o s in shaping he aginal mic obiome du ing meno-
pause. By gainingmo e insigh in o hese dynamics, we can de elop a ge ed
in e en ions o p omo e aginal heal h and mi iga e he isk o in ec ions in
menopausal women.
Ho mone-mic obiome c oss alk in women´s aging
Es ogen is he p ima y sex ho mone associa ed wi h endoc inological
ansi ions in women, including pube y, p egnancy, and menopause108.
Al hough mic obiome di e si y dec eases as we age, o he ac o s dic a e he
mic oe olu ion o he mic obial communi y a each body si e, such as die ,
habi s, hos de enses, and ho monal le els. Du ing he menopause ansi-
ion, women’s mucosal issues a e hin and d y, leading o dysbiosis in
aginal and o al bac e ia ha can be mi iga ed by menopausal ho mone
he apy60. The mic obiome and sex ho mones ha e a dynamic bidi ec ional
in e ac ion ha changes wi h in insic ac o s such as aging (Fig. 3).
Es ogen le els in he human body a e egula ed h ough a balance be ween
ee es ogen, which can be di ec ly u ilized by cells and es ogen bound o
p o eins (conjuga ed es ogen) wi h a hal -li e longe han he o me , se -
ing as a ese oi o a ailable es ogen. Es obolome bac e ia can decon-
juga e es ogen and ans o m i in o i s ac i e o m, hus able o bind o
es ogen ecep o s and a ec all es ogen-dependen p ocesses72,109.Thisis
defined as he collec ion o mic oo ganisms and hei genes capable o
me abolizing es ogen. Recen ly, he abili y o gas oin es inal ac bac e ia
o me abolize p o ein-bound es ogen has been desc ibed using he bac e ial
enzyme β-glucu onidase105,110. F ee es ogen can be anspo ed o many
si es, such as he agina, and p omo e Lac obacillus dominance in he
mic obio a72. The e o e, mic oo ganisms me abolizing sex ho mones could
change hos con ol in a ailabili y and, hus, physiological p ocesses ela ed
o ho mones. Howe e , i emains unclea how he mic obial genes in e ac
wi h he hos in aging o ho monal fluc ua ion a mul iple body si es.
Es ogen le els du ing menopause dec ease due o educed o a ian
p oduc ion. Du ing he menopausal ansi ion pe iod, sex ho mones can
inc ease, leading o inflamma ion o o al issues and mic obial dysbiosis in
gingi al issues. Fu he mo e, in o he egions o he gas oin es inal ac ,
such as he in es ine, es ogen le els ha e a egula o y e ec on hos -
mic obio a balance111. The o al-gu -es obolome axis sugges s a connec ion
be ween sys emic es ogens and o al heal h109. Ce ain mic oo ganisms in he
o al mic obio a can also modula e s e oid ho mone le els by deg ading and
me abolizing hem. Thus, ea ly signs o es ogen- ela ed issues may mani es
as o al dysbiosis, highligh ing he impo ance o moni o ing o al bac e ia. Fo
example, in i o s udies ha e shown ha p oges e one has a dose-dependen
bac e ios a ic o bac e icidal e ec agains Neisse ia and S aphylococcus spp,
bac e ia ound in he o al mic obio a o humans. O he species such as
T eponema den icola use s e oids de i ed om he hos as g ow h ac o s, a
phenomenon ha can be ela ed o i s i ulence112.Simila ly,es ogenand
p oges e one ac as eplacemen g ow h ac o s o he K i amin, an essen ial
nu ien o Bac e oides species such as P e o ella in e media,P e o ella
nig ecens,andCapnocy ophaga, which inc eases in gingi al issue con-
comi an ly wi h es adiol and p oges e one cycles113. A ecen s udy
h ps://doi.o g/10.1038/s44294-024-00050-y Re iew
npj Women's Heal h | (2025) 3:3 7
in es iga ed he impac o es adiol, es iol, p oges e one, o es os e one on
in i o o al biofilms o induce he exp ession o i ulence ac o s. The s udy
e ealed minimal e ec s on biofilm o ma ion, mic obial composi ion, and
p o eoly ic ac i i y114. In o al gingi al issues, he gingi a con ains a ecep o
capable o specifically binding es ogen, and i s mic obio a has
β-glucu onidases (GUS) as es ogen-me abolizing enzymes. The GUS a las
de i ed om he human o al mic obiome was associa ed wi h 53 unique
GUS enzymes. Many o hese enzymes we e iden ified in gene a commonly
associa ed wi h pe iodon al disease, such as Tanne ella,T eponema,P e-
o ella,andFusobac e ium. In pa icula , he GUS p o eins ound in he o al
mic obiome we e di e en om hose ound in he gas oin es inal ac 115.
Howe e , he p ecise mechanisms unde pinning he influence o sex ho -
mones in o al niches emain a subjec o ongoing explo a ion.
Es one is a c i ical es ogen ho mone du ing menopause, p ima ily
p oduced by ex ao a ian issues as o a ian unc ion educes75.I sinfluence
on menopausal symp oms, such as ho flashes, u ogeni al a ophy, and
changes in bone densi y, unde sco es i s significance. In i o s udies ha e
iden ified he genes OecA, OecB, and OecC ha play a pi o al ole in he
deg ada iono es ogenwi hin hebac e iumSphingomonas sp. KC8. OecA
encodes 3β,17β-hyd oxys e oid dehyd ogenase, ini ia ing es ogen b eak-
down. OecB, which encodes es one-4-hyd oxylase, acili a es he con e -
sion o es one in o an in e media e compound. OecC, esponsible o
4-hyd oxyes one 4,5-dioxygenase, u he p ocesses hese in e media e
compounds116. I should be no ed ha he Sphingomonas s ain KC8 was he
fi s genome epo o es ogen-deg ading bac e ia117. Howe e , Sphingo-
monas is no ound o be a esiden bac e ium in he human mic obiome,
bu a he an oppo unis ic nosocomial in ec ion.
The disco e y o he abili y o endogenous s e oids o di ec ly igge
al e a ions in he no mal mic obio a o e s no el insigh s in o he link o o al
and gene al heal h ma ked by fluc ua ions in s e oid le els118.S e oiddehy-
d ogenases ha e been iden ified in se e al bac e ial gene a including Clos-
idium, Co ynebac e ium, Bacillus, Mycobac e ium, Noca dia,
Pseudomonas, and S ep omyces119. I highligh s ha he inhabi an s o o al
mic obial cells can me abolize p oges e one and es os e one h ough
mic obial enzymes. S ep ococcus mu ans possesses bo h 5α-and5β-s e oid
educ ases, alongside 3α-, 17β-, and 20α-hyd oxys e oid dehyd ogenases,
acili a ing he me abolism o p oges e one and es os e one120.Inaddi ion,
o he o al bac e ia ound in he gingi al sulcus a e known o ha bo bac e ial
enzymes in ol ed in s e oid con e sion. Fo example, T eponema den icola
me abolizes choles e ol, p oges e one, and es os e one h ough 5α- educ-
ase, 3β-, and 17β-hyd oxys e oid dehyd ogenase112. Thus, ocusing on he
mic obial ole in ho monal me abolism du ing he menopausal ansi ion
unde sco es he po en ial o a ge ed in e en ions and sheds ligh on p e-
iously unexplo ed a enues o he managemen o menopausal symp oms.
Asignifican limi a ion o cu en menopausal mic obiome esea ch is
he o e ep esen a ion o Wes e n popula ions leading o a lack o di e si y
in he s udied g oups121–123.Thisbiasmaylimi hegene alizabili yo
findings, as he mic obiome is known o be influenced by li es yle, die , and
geog aphic ac o s ha can a y significan ly be ween popula ions124.S u-
dies ha e shown ha he gu mic obiome, in pa icula , is shaped by ac o s
such as die and en i onmen , which can di e d as ically be ween Wes e n
and non-Wes e n popula ions. Fo example, women in A ican o Eas e n
egions may ha e dis inc mic obial p ofiles due o di e ences in hei die s
and exposu es o en i onmen al ac o s125. Add essing his gap is c ucial.
Resea ch ha includes mo e di e se popula ions, such as hose om A ica,
Asia, and La in Ame ica, could o e a mo e comp ehensi e unde s anding
o how menopause a ec s he mic obiome globally. A mo e geog aphically
inclusi e app oach would help e eal a ia ions in mic obial communi ies,
allowing o he de elopmen o mo e pe sonalized in e en ions ha a e
be e sui ed o he needs o di e se g oups o menopausal women.
Conclusion
Menopause ma ks a significan poin in he aging p ocess o women, cha -
ac e ized by ho monal shi s and he cessa ion o mens ual cycles, impac ing
hei heal h and well-being. Pe imenopause ep esen s a p olonged me abolic
ansi ion ha conce ns he in e ac ion be ween ho mones and he mic o-
biome. This phase o a woman’s li e, which spans p emenopausal ho mone
le els h ough he menopausal ansi ion, significan ly impac s he compo-
si ion and dynamics o he mic obiome. The g adual decline in ho mone
le els du ing pe imenopause dis up s he balance o he mic obiome, leading
o a a ie y o ana omical condi ions and heal h complica ions. The mic o-
biome unde goes significan changes impac ing a ious body si es including
he o al, in es inal, and u ogeni al niches. Ho monal fluc ua ions play a
c ucial ole in shaping hese mic obial communi ies, wi h implica ions o
disease suscep ibili y. Es ogen influences mic obial communi ies while
mic obes can me abolize and influence es ogen le els. Thus, he in e ac ion
be ween ho mones and he mic obiome is complex and bidi ec ional.
Unde s anding he menopausal shi encompasses how ho monal changes,
en i onmen al ac o s, and mic obial dynamics a ec menopausal symp oms
and women’s heal h. This insigh could d i e he de elopmen o p ecise
he apies o alle ia e symp oms and minimize he isk o ela ed heal h issues,
ul ima ely enhancing he quali y o li e o menopausal women.
Da a a ailabili y
No da ase s we e gene a ed o analysed du ing he cu en s udy.
Recei ed: 26 Augus 2024; Accep ed: 30 Decembe 2024;
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