Vaginal and vestibular tissues are not passive recipients of hormones from the bloodstream. They contain steroid receptors and enzyme systems that allow sex steroids to be produced and used locally from circulating precursors such as DHEA.

This local hormone biology is called intracrinology.[1,2]

The strongest direct experimental evidence comes from human postmenopausal vaginal tissue: researchers have shown that vaginal cells can take up DHEA, convert it into testosterone and dihydrotestosterone (DHT), and activate androgen-receptor-dependent genes.[3]

The vulvar vestibule—the tissue immediately surrounding the vaginal opening—also has substantial androgen and estrogen receptor expression and is described in the clinical literature as possessing steroid-metabolizing machinery relevant to DHEA signaling.[4–6]

The evidence is therefore no longer simply “vaginal findings might apply to the nearby vulva.”

We have evidence specific to the vestibule.

What we do not yet have is the vestibular equivalent of the strongest vaginal experiment: isolated human vestibular cells exposed to DHEA with downstream testosterone, DHT and estrogen production directly quantified by mass spectrometry.

That distinction tells us both what is established and what remains to be studied.

Key points

• Intracrine signaling means active hormones are formed locally from precursor molecules within the tissues that use them.

• Human postmenopausal vaginal tissue can directly convert DHEA into testosterone and DHT.[3]

• Androgen receptors are present throughout the vulva, vestibule, clitoris and vagina and are particularly abundant in several vulvar and vestibular compartments.[4,5]

• Human vestibular tissue is therefore hormonally responsive in its own right; it should not be treated simply as an extension of the vagina.

• Vaginal DHEA has also produced measurable changes in vestibular tissue and pain in a small human pilot study.[6]

• Postmenopausal vaginal tissue appears to have very limited capacity to manufacture DHEA from cholesterol de novo, while retaining substantial machinery for using DHEA supplied to it.[3]

• Circulating DHEA availability declines substantially with age—by an average of roughly 60% from peak young-adult levels by the time of menopause in published estimates.[2]

• Blood hormone measurements do not directly measure steroid production or receptor activation occurring inside vaginal or vestibular cells.

How do hormones normally reach tissue?

The familiar endocrine model works like this:

gland → bloodstream → distant tissue

The ovaries produce estradiol. Estradiol circulates through the blood. Cells expressing estrogen receptors respond to it.

That is endocrine signaling.

But some tissues have another capability.

Instead of waiting for an endocrine gland to deliver a fully active sex steroid, they can take up a circulating precursor and convert it locally into an active hormone.

That is where DHEA becomes important.

What does “intracrine” mean?

The term intracrinology was developed to describe the formation of active hormones inside peripheral target tissues from circulating precursors.[1]

In simplified form:

DHEA-S ↔ DHEA → androstenedione → testosterone → DHT

And, in cells containing sufficient aromatase:

androstenedione → estrone

testosterone → estradiol

The exact products formed depend on which enzymes are expressed by the particular cell.

That is an important feature of intracrine biology: different tissues—and even different cell types within the same tissue—do not necessarily make the same hormones from the same precursor.

Signaling mode	Where the active signal originates	Where it acts
Endocrine	Distant gland	Target tissue reached through circulation
Paracrine	Nearby cell	Neighboring cells
Autocrine	Same cell	Back on that cell
Intracrine	Formed inside the target cell from precursor	Primarily within the cell in which it is formed

In classical intracrine steroid physiology, active androgens and estrogens are formed, act on their receptors, and are then largely metabolized locally before their inactive metabolites leave the tissue.[1,2]

This is why intracrine activity cannot simply be inferred from a blood testosterone or estradiol measurement.

What is DHEA, and why does it matter?

DHEA—dehydroepiandrosterone—is a steroid produced predominantly by the adrenal glands, much of it circulating as its sulfated reservoir form, DHEA-S.

Its importance here is primarily as precursor substrate.

DHEA is not the final androgen or estrogen signal.

It is material from which appropriately equipped cells can make those signals.

DHEA is not simply a message. It is material.

DHEA availability also changes substantially with age.

Published intracrinology data estimate that DHEA secretion has fallen by an average of approximately 60% from peak young-adult levels by the time of menopause, with continued decline thereafter.[2]

At the same time, ovarian estradiol production falls dramatically at menopause.

Peripheral intracrine steroid production therefore becomes particularly important during postmenopausal life.[2]

What has actually been demonstrated in human vaginal tissue?

This is where the evidence becomes unusually direct.

In 2021, Cellai and colleagues studied vaginal tissue obtained from postmenopausal women and cultured human vaginal smooth-muscle cells.[3]

They measured steroidogenic enzymes, steroid receptors, actual hormone production and downstream androgen-receptor activity.

They found four important things

Finding	What the researchers demonstrated
The conversion machinery is present	Vaginal tissue and cells expressed multiple enzymes capable of metabolizing DHEA downstream through androgen pathways
DHEA was converted into active androgens	DHEA exposure produced androstenedione, testosterone and DHT, measured by LC-MS/MS
The newly generated androgens were biologically active	DHEA induced androgen-responsive genes
The effect depended on the androgen receptor	Blocking the androgen receptor prevented several DHEA-induced gene responses

The receptor findings were also striking.

In whole vaginal tissue, estrogen receptor alpha was the most highly expressed steroid receptor measured.

But in isolated human vaginal smooth-muscle cells, the androgen receptor was the most highly expressed steroid receptor studied.[3]

This tells us something important about genital tissue biology:

The vagina is both a hormone-responsive tissue and a tissue capable of locally producing active androgens from precursor substrate.

It also shows why whole-tissue averages can be misleading. Epithelium, smooth muscle, blood vessels, connective tissue and nerves may have different receptor profiles and different functions.

Can vaginal tissue make its own DHEA?

Not efficiently, based on the human postmenopausal tissue studied so far.

Cellai and colleagues found very low expression of the enzymes required for the earliest steps of steroid synthesis from cholesterol—including STAR, CYP11A1 and CYP17A1—compared with ovarian tissue.[3]

By contrast, the tissue expressed substantial downstream machinery for using DHEA once it was available.

It also expressed steroid sulfatase, which can convert circulating DHEA-S back toward usable DHEA.[3]

The most accurate interpretation is therefore:

Postmenopausal vaginal tissue appears to have little capacity to synthesize meaningful quantities of DHEA de novo, but substantial capacity to metabolize DHEA that reaches it.

That creates a distinction between two components of local hormone biology:

conversion capacity — what enzymes the tissue has;

and

substrate availability — how much precursor reaches those enzymes.

A tissue can retain its conversion machinery while the amount of precursor available to enter that machinery declines.

What about the vulvar vestibule?

This is where the evidence has become much more interesting.

The vulvar vestibule is the tissue inside the labia minora surrounding the urethral and vaginal openings.

It is anatomically and developmentally distinct from both the vaginal canal and the more external keratinized vulvar skin.

If you are not completely clear on where these structures are, see All About the Vulva before going further.

The vestibule contains steroid receptors

Human vestibular biopsy studies have directly demonstrated expression of:

• androgen receptors;

• estrogen receptor alpha;

• estrogen receptor beta;

• progesterone receptors; and

• glucocorticoid receptors.[4]

A broader review of human vulvovaginal tissue found androgen receptors throughout the:

• labia majora;

• labia minora;

• vestibule;

• clitoris; and

• vagina.[5]

Androgen receptors were particularly abundant in several vulvar compartments, including epidermal keratinocytes and dermal fibroblasts of the labia and vestibule.[5]

So the vestibule is not merely anatomically close to androgen-responsive tissue.

It is androgen-responsive tissue.

What about intracrine enzymes in the vestibule?

The vestibular literature describes vestibular cells as possessing steroid-metabolizing machinery capable of participating in local DHEA metabolism.[5,6]

But the level of evidence should be distinguished from the Cellai vaginal experiment.

In vaginal cells, investigators directly added DHEA and measured downstream testosterone and DHT by mass spectrometry.[3]

An equivalent experiment has not yet been published in isolated human vestibular cells.

So the evidence currently looks like this:

Vestibular steroid receptors: directly demonstrated in human tissue.[4,5]

Vestibular steroid-metabolizing machinery: supported and described in the human vulvovaginal literature.[5,6]

Direct DHEA → testosterone/DHT quantification in isolated vestibular cells: not yet demonstrated.

That missing experiment is important because the vestibule should not be assumed to metabolize DHEA in exactly the same proportions as vaginal smooth muscle.

Vaginal DHEA can nevertheless affect the vestibule

There is another kind of human evidence.

In 2023, Goldstein, Goldstein and Kim studied 11 menopausal women with moderate-to-severe dyspareunia who used 6.5 mg intravaginal prasterone—pharmaceutical DHEA—daily for 20 weeks.[6]

Unlike the large vaginal prasterone trials, this study deliberately examined the vestibule.

The investigators measured:

• cotton-swab pain at vestibular sites;

• vestibular tissue appearance;

• vaginal tissue appearance;

• serial vulvoscopic photographs; and

• pain during sexual activity.

Vestibular pain progressively improved, reaching statistical significance at 16 weeks.

Vestibular tissue scores improved significantly.

And all 11 women showed improvement in photographed vestibular erythema and pallor by the end of the study.[6]

This was a small, open-label pilot study, so it does not establish efficacy with the strength of a randomized controlled trial.

But it provides an important anatomical observation:

A DHEA treatment placed inside the vagina produced measurable biological changes in the vestibule outside the vaginal canal.

The investigators proposed that prasterone leaving the vagina came into contact with vestibular tissue and was metabolized locally.[6]

Current recommendations from the Fifth International Consultation on Sexual Medicine also recognize the dual estrogenic-androgenic intracrine activity of vaginal DHEA and note that this may be relevant when the vestibule is particularly involved in GSM symptoms.[7]

For the complete evidence trail—including the critical difference between vaginal, vestibular and external vulvar delivery—see DHEA for the Vulva: What the Evidence Actually Shows.

Does vaginal tissue make estrogen or androgens from DHEA?

The answer depends on the cell.

That is the point of intracrinology.

In the human vaginal smooth-muscle cells studied by Cellai and colleagues, DHEA metabolism was predominantly androgenic.[3]

The cells readily generated androstenedione, testosterone and DHT.

Aromatase expression was extremely low in that experimental system, and estradiol was not detected after DHEA exposure.[3]

That does not mean that all vaginal or vulvar cells convert DHEA predominantly into androgens.

Other cell populations can express different enzyme combinations.

A more accurate conclusion is:

Human vaginal smooth-muscle cells have been directly shown to use DHEA predominantly through androgen-producing pathways. The steroid output of other genital cell types—including vestibular epithelial cells—has not been characterized with the same precision.

This cell-specificity is not a weakness of the intracrine model.

It is one of its defining features.

Why are androgens relevant to female genital tissue?

Because these tissues contain androgen receptors, and androgen-receptor signaling produces biological effects that are not identical to estrogen-receptor signaling.

Experimental and human-tissue literature implicates androgen signaling in aspects of:

• smooth-muscle function;

• nitric-oxide signaling;

• vascular responsiveness;

• genital tissue architecture;

• clitoral and vestibular biology;

• sensory function; and

• sexual arousal physiology.[3,5,8]

Estrogen also influences several of these systems.

The correct distinction is therefore not:

estrogen = structure
androgen = function

The biology overlaps.

The more accurate statement is:

Estrogens and androgens act through different receptors and generate partly overlapping but nonidentical signals within genital tissue.

This is why supplying estradiol does not automatically reproduce androgen-receptor signaling.

Estradiol cannot activate the androgen receptor.

And steroid conversion does not run backward:

DHEA → androstenedione → testosterone → DHT

and

testosterone → estradiol

but:

estradiol ✕→ testosterone

Increasing estradiol therefore does not regenerate DHEA, testosterone or DHT.

For a deeper explanation of why that distinction can matter clinically, see Why Estrogen Isn’t Enough for Midlife Vaginal Tissue Health.

Why doesn’t a blood test tell us what the tissue is doing?

Because blood and intracellular steroid activity are different biological compartments.

A serum DHEA-S measurement tells us how much DHEA-S is circulating.

A serum testosterone measurement tells us how much testosterone is circulating.

Neither directly tells us:

• how much DHEA entered a vestibular or vaginal cell;

• how much steroid sulfatase that cell expresses;

• how much DHEA it converted into androstenedione;

• whether testosterone was converted into DHT or estradiol;

• how abundant its androgen or estrogen receptors are;

• how strongly those receptors were activated; or

• how quickly the locally generated steroid was inactivated.

That is why there is currently no routine clinical blood test for vaginal or vulvar intracrine activity.

Normal circulating hormone levels and abnormal tissue function are not mutually exclusive.

But the reverse is also important:

A low serum DHEA or testosterone value does not, by itself, prove inadequate intracrine activity in a particular tissue.

We currently cannot measure that directly in routine clinical practice.

How does this relate to vaginal dryness and GSM?

Genitourinary syndrome of menopause is frequently described primarily through estrogen deficiency.

Estrogen loss is unquestionably important.

But the vulva, vestibule, vagina, urethra and clitoris are not estrogen-only tissues.

They contain multiple steroid receptors, and some of these tissues retain the ability to locally metabolize precursor hormones after ovarian estrogen production has declined.[3–5]

That does not mean androgen deficiency explains every case of dryness, pain or altered sensation.

Vulvovaginal symptoms can also involve:

• epithelial change;

• altered hydration;

• connective tissue;

• vascular function;

• sensory nerves;

• pelvic-floor dysfunction;

• inflammation;

• dermatologic disease;

• infection;

• medications; and

• central sexual-response pathways.

For the broader tissue biology of dryness, see What Causes Vaginal Dryness After Menopause?.

And for the larger clinical syndrome, see Genitourinary Syndrome of Menopause: A Tissue-Level View.

Frequently asked questions

Does the vagina actually make hormones?

Yes.

Human postmenopausal vaginal cells have been directly shown to convert DHEA into androstenedione, testosterone and DHT.[3]

The active androgens produced can then activate androgen-receptor-dependent cellular responses.

Does the vulvar vestibule make hormones too?

The vestibule contains androgen and estrogen receptors and is described as possessing steroid-metabolizing machinery relevant to local hormone metabolism.[4–6]

What has not yet been done is the same direct biochemical experiment performed in vaginal smooth-muscle cells: exposing isolated human vestibular cells to DHEA and quantifying the resulting sex steroids by mass spectrometry.

So intracrine activity in the vestibule is strongly biologically supported, but its precise DHEA metabolic output has not been characterized as directly as that of the vagina.

Does the tissue make its own DHEA?

Human postmenopausal vaginal tissue appears to have very limited capacity to synthesize DHEA from cholesterol de novo.[3]

It is much better equipped to use DHEA or DHEA-S supplied from outside the cell.

Whether every vulvar compartment has exactly the same precursor dependence has not been directly established.

Does intracrine hormone production stop at menopause?

No.

The machinery for local steroid metabolism remains present in postmenopausal vaginal tissue.[3]

What changes substantially is the endocrine environment—including loss of ovarian estrogen production and the progressive age-related decline in DHEA availability.[2]

Can I test my intracrine hormone activity?

Not with a routine clinical test.

There is currently no validated blood, urine or saliva test that directly measures androgen or estrogen production inside vulvar, vestibular or vaginal cells.

If my testosterone is normal, does that mean my genital tissue has enough androgen signaling?

Not necessarily.

Serum testosterone does not directly measure intracellular DHEA conversion, local DHT formation, receptor abundance or androgen-receptor activation.

But a normal serum level also should not be interpreted as evidence that tissue androgen activity is deficient.

The tissue compartment simply is not directly measurable with routine testing.

Does DHEA always become testosterone?

No.

What DHEA becomes depends on the enzymes expressed by the receiving cell.

It can enter pathways leading toward androstenedione, testosterone, DHT, estrone or estradiol.

In the human vaginal smooth-muscle cells studied by Cellai et al., the measured output was predominantly androgenic.[3]

Is vaginal DHEA evidence the same thing as evidence for vulvar DHEA?

No.

Anatomical route matters.

Intravaginal prasterone has randomized clinical-trial evidence and an established regulatory indication. The 2023 pilot also shows that intravaginal DHEA can affect vestibular tissue.[6]

But those findings do not establish the pharmacokinetics, dose or efficacy of DHEA applied directly to the external vulva or vestibule.

Those routes require direct study.

What is established—and what remains uncertain?

Established

• Intracrine steroid formation occurs in peripheral human tissues.[1,2]

• DHEA is an important precursor for postmenopausal peripheral sex-steroid formation.[2]

• Human postmenopausal vaginal tissue contains substantial downstream steroid-metabolizing machinery.[3]

• Human vaginal smooth-muscle cells can convert DHEA into androstenedione, testosterone and DHT.[3]

• Those locally generated androgens can produce androgen-receptor-dependent cellular responses.[3]

• Human vestibular tissue expresses estrogen and androgen receptors.[4,5]

• Androgen receptors are distributed throughout the vulva, vestibule, clitoris and vagina.[5]

• DHEA availability declines substantially with age.[2]

• Intravaginal prasterone can produce measurable changes in vestibular tissue as well as vaginal tissue.[6]

Supported, but less directly characterized

• The vestibule contains steroid-metabolizing machinery capable of supporting local intracrine DHEA metabolism.[5,6]

• Androgen signaling contributes to multiple aspects of genital tissue biology beyond epithelial estrogen signaling.[3,5,8]

Inferred or proposed

• Individual variation in DHEA availability or local enzyme expression may contribute to differences in vulvovaginal symptoms or treatment response.

• In some women, an incompletely addressed androgen-responsive pathway may contribute to symptoms that persist despite adequate estrogen treatment.

These hypotheses are biologically coherent but are not currently diagnostic conclusions.

Not established

• The exact steroid products generated from DHEA by human vestibular cells.

• A clinical test of vaginal or vestibular intracrine capacity.

• A serum DHEA, testosterone or estradiol threshold that defines adequate local tissue signaling.

• That low DHEA explains every case of GSM, vulvar pain, reduced sensation or incomplete response to estrogen.

• That pharmacokinetic or efficacy findings from intravaginal DHEA can automatically be applied to DHEA placed directly on external vulvar or vestibular tissue.

The central idea

Female genital tissues are not passive hormone targets.

They contain receptor systems and local steroid-metabolizing machinery that allow the hormonal environment inside the tissue to differ from what a blood test alone would suggest.

Human vaginal tissue provides the clearest direct example: DHEA can enter vaginal cells, be converted into testosterone and DHT, activate the androgen receptor, and then be locally metabolized.[3]

The vulvar vestibule also has substantial steroid-receptor biology and evidence of local hormone responsiveness.[4–7]

So the old model:

blood hormone level → tissue response

is incomplete.

A more accurate model includes:

circulating precursor → tissue uptake → cell-specific enzyme conversion → local receptor activation → local metabolism

That is intracrinology.

And it gives us a much more precise way to ask the next scientific question:

Not simply “How much hormone is in the blood?” but “What can this particular tissue make, from the substrate available to it, and what does it do with the result?”

---

By Laura Kelly, DAOM, L.Ac., Dipl. O.M. — A California-licensed primary care provider and nationally board-certified clinician with a clinical focus on women’s health and healthy aging. Research Scholar, Ronin Institute. ORCID: 0000-0001-6586-7308. More about Dr. Kelly

Last scientifically reviewed: August 2026

Educational note: This article provides general scientific education and is not a diagnosis or individualized treatment recommendation. Persistent or new vulvar, vaginal, urinary, sexual or sensory symptoms should be evaluated by an appropriately qualified healthcare provider. Hormonal treatment decisions should be made with a clinician familiar with the individual’s medical history.

References

1. Labrie F. Intracrinology. Molecular and Cellular Endocrinology. 1991;78(3):C113–C118. doi:10.1016/0303-7207(91)90116-A

2. Labrie F. Intracrinology and menopause: the science describing the cell-specific intracellular formation of estrogens and androgens from DHEA and their strictly local action and inactivation in peripheral tissues. Menopause. 2019;26(2):220–224. doi:10.1097/GME.0000000000001177

3. Cellai I, Di Stasi V, Comeglio P, et al. Insight on the intracrinology of menopause: androgen production within the human vagina. Endocrinology. 2021;162(2):bqaa219. doi:10.1210/endocr/bqaa219

4. Johannesson U, Sahlin L, Masironi B, Rylander E, Bohm-Starke N. Steroid receptor expression in the vulvar vestibular mucosa—effects of oral contraceptives and menstrual cycle. Contraception. 2007;76(4):319–325. doi:10.1016/j.contraception.2007.06.014

5. Palacios S. Expression of androgen receptors in the structures of vulvovaginal tissue. Menopause. 2020;27(11):1336–1342. doi:10.1097/GME.0000000000001587

6. Goldstein SW, Goldstein I, Kim NN. Vestibular tissue changes following administration of intravaginal prasterone: a vulvoscopic open-label pilot study in menopausal women with dyspareunia. Sexual Medicine. 2023;11(3):qfad028. doi:10.1093/sexmed/qfad028

7. Simon JA, Nappi RE, Chedraui P, et al. Genitourinary syndrome of menopause (GSM): recommendations from the Fifth International Consultation on Sexual Medicine (ICSM 2024). Sexual Medicine Reviews. 2026;14(1):qeaf055. doi:10.1093/sxmrev/qeaf055

8. Traish AM, Vignozzi L, Simon JA, Goldstein I, Kim NN. Role of androgens in female genitourinary tissue structure and function: implications in the genitourinary syndrome of menopause. Sexual Medicine Reviews. 2018;6(4):558–571. doi:10.1016/j.sxmr.2018.03.005