When the Dermatology Playbook Meets the Testosterone Conversation

In an era when the importance of testosterone as a female hormone is gaining traction both on social media and with the FDA, we dermatologists are finding ourselves in unfamiliar waters. We have been trained in the art of blocking androgens due to their cutaneous consequences, like female hormonal acne, female pattern hair loss, and hirsutism. For decades, we have used medications like combination oral contraceptive pills, several of which have an FDA indication for acne, and spironolactone to raise SHBG and block androgen receptors. We have been doing so with great success, with the recent FASCE trial in Acta Dermato-Venereologica demonstrating spironolactone’s non-inferiority to doxycycline for adult female acne, alongside the larger SAFA trial in the BMJ that has solidified spironolactone’s position as a first-line systemic option.

But more and more frequently, I’m having a very different conversation with women in my practice approaching me for help with these androgen-mediated skin and hair concerns. They are saying no thank you to birth control pills, and what else you got, doc, to spironolactone.

These women are reading. They’re listening. They’re paying attention to the growing body of work and the cultural recognition that women have and need testosterone. Testosterone plays female-specific roles in libido, energy, mood, cognition, bone, muscle, and the genitourinary tissues. They’re watching the FDA inch closer to approving a female testosterone formulation. And they’re showing up in my office, in their 40s, declining the medications that for decades were our default answer.

There are also women who are not yet informed — women who assume their ever-expanding list of symptoms, from low libido to frequent urination to fatigue, is just part of getting older. These are the women we must educate and counsel, so that in treating a dermatologic problem, we don’t make another part of their lives much worse. These women aren’t saying what else you got, doc. They’re saying yes to whatever we offer, because no one has told them there is a question to ask.

I think they’re right to ask the question. And I think we have to be ready with a better answer than the one we’ve been giving. We also need to be retrained in what questions we ask our patients to aid shared decision-making around blocking androgen hormones. Then we can offer an answer that holds the strength of the evidence base for spironolactone and weighs the real cost of layering an antiandrogen on top of an already androgen-depleted woman.

The mechanism, briefly, is the trade-off

Spironolactone’s full receptor pharmacology is beyond the scope of this article, but here is the short version because the mechanism is the issue.

At our dermatologic doses (25–200 mg/day), spironolactone produces its cutaneous benefit through four converging mechanisms: direct androgen receptor blockade in the sebocyte and dermal papilla, inhibition of cutaneous 5α-reductase, modest inhibition of adrenal and ovarian androgen biosynthesis, and a rise in SHBG that lowers free testosterone. The skin responds because the androgen signal at the pilosebaceous unit drops.

But the androgen receptor doesn’t only live in sebaceous glands and hair follicles. It is densely expressed in the vulvar vestibule, the vaginal epithelium, the urethra, the clitoris, the brain, bone, and muscle. Spironolactone does not selectively block the “bad” androgen effects (acne, hirsutism, hair loss) and leave the “good” ones (libido, vestibular trophism, energy, mood) alone. It blocks androgen activity. Period. The skin benefit and the systemic cost come from the same mechanism.

This is the part of the conversation that has been underweighted in dermatology for years. And it is the part that the women walking into my office have figured out without us.

What this looks like in a perimenopausal woman

By the time a woman is in her 40s, her testosterone has already dropped to roughly half of what it was in her 20s. This decline happens gradually over decades and is not caused by menopause. It’s a function of aging ovarian and adrenal output. Estradiol fluctuates wildly and eventually crashes. Progesterone declines. Testosterone decreases more gradually and does not fall off a cliff at menopause as does estrogen. This contributes to a relative androgen excess state — testosterone is lower than it was in our 20s, but still relatively high compared to our estrogen. Hence, the acne in our 40s and hair thinning on our scalp, while it thickens on our upper lip. Reaching for an androgen blocker in this state of relative androgen excess makes mechanistic sense.

But what if the 45-year-old woman sitting before us is not only experiencing the skin issues of relative androgen excess, but also the issues of overall androgen decline? These two opposing realities can be true at the same time. We see her acne and hair loss, but unless we ask, she may not tell us about her libido or dyspareunia. After all, we are dermatologists, and what could libido possibly have to do with her acne?

Let’s say she doesn’t bring it up either, goes on spironolactone for her hormonal acne, does very well, but also ends up with frequent UTIs, worsening pain with sex, and an even further compromised libido. She sees her PCP, her gyno, her urologist. One of them finally sees spironolactone on her medication list. Her acne medication that so beautifully cleared her skin is wreaking havoc on her genitourinary and sexual health.

She’s upset. The dermatologist feels terrible. But you don’t know what you don’t know. The acne, as predicted, improved. Her quality of life suffered.

The symptoms of low androgen activity in women — low libido, fatigue, blunted motivation, low mood, brain fog, and genitourinary changes — overlap almost perfectly with the symptoms of perimenopause itself. That overlap is the problem. It means the side effects of spironolactone are often invisible. The woman attributes them to her age, her hormones, her stress, her marriage, her job. Her dermatologist attributes them to perimenopause. Nobody connects them to the medication.

The numbers we actually have

Decreased libido affects roughly 10–15% of women on spironolactone, dose-dependent and reversible with dose reduction or discontinuation. Vaginal dryness and introital dyspareunia affect approximately 15–25% — the side effect, I think, deserves the most attention, and gets the least.

The vulvar vestibule and the glands that produce introital lubrication are androgen-dependent for their trophism. Blocking the androgen receptor in this tissue produces vestibular atrophy and reduced lubricant output. A 2019 case series by Goldstein and colleagues in Sexual Medicine documented hormonally-associated vestibulodynia and female sexual arousal disorder caused or exacerbated by spironolactone — patients who had been seen by multiple clinicians and prescribed antifungals, neuromodulators, and topical steroids before anyone recognized the medication as the trigger. Resolution required stopping the spironolactone and, in most cases, topical compounded estradiol/testosterone gel to the vestibule.

What we do not have is a clean prospective study of perimenopausal women on dermatologic-dose spironolactone with serial validated sexual function measures, on-therapy testosterone tracking, and stratification by menopausal status. The 15–25% figure is almost certainly an undercount, because the baseline rate of GSM in perimenopausal women is already climbing. This is a knowledge gap, and I won’t pretend otherwise.

Genitourinary syndrome of menopause, when spironolactone is in the picture

GSM is primarily an estrogen-deficiency syndrome. But the androgen contribution to vulvar, vaginal, and urethral tissue is real and increasingly recognized as essential to vestibular and clitoral health.

So when a perimenopausal woman on spironolactone tells me that she’s drier, more irritated, that sex hurts more than it did six months ago, I take that seriously as a possible drug effect, not just a coincidence of timing. Layering an androgen receptor blocker on top of declining ovarian production can convert subclinical GSM into symptomatic GSM, or worsen existing symptoms.

This is not a contraindication to spironolactone in my practice. It is a reason to counsel about it explicitly and co-manage proactively.

Vaginal estradiol cream is the reasonable first move. It’s safe, locally acting, well-studied, and addresses the estrogen-mediated piece of GSM directly. It will help with the dryness, the tissue thinning, and the urinary symptoms. For many women, it’s enough.

But it has a limitation worth naming. Vaginal estradiol does not replace androgen activity. If a woman’s symptoms — particularly clitoral or vestibular symptoms, arousal difficulty, loss of sensation — are being driven in part by androgen blockade, vaginal estrogen alone may underperform expectations. Intravaginal DHEA (prasterone) is converted locally to both estrogens and androgens and is increasingly preferred by some clinicians in women on antiandrogens. Compounded topical estradiol/testosterone gel to the vestibule is what Goldstein’s group used to resolve spironolactone-associated vestibulodynia, and it remains a reasonable option in the right patient with the right prescriber.

“Add vaginal estrogen” is a starting point, not a complete answer. We owe women better than a reflexive single prescription when the underlying pharmacology calls for a more layered conversation.

Can we just give testosterone back?

This is the question I get often, and it’s the right question to ask. At the Let’s Talk Menopause Menoposium in Boston, I asked a panel of expert physicians how we can best manage the side effects caused when we prescribe androgen blockers. Dr. Corinne Menn stated very clearly, “You give the hormones back.”

But this begs a question. If spironolactone is blocking the androgen receptor, can we simply add testosterone therapy and have it work? Or did she mean something different — that we give the androgens back by taking the spironolactone away?

The honest answer is that putting a woman on testosterone to fix the testosterone blockade of spironolactone probably won’t work well. Mechanistically, you’re working against yourself. Spironolactone is competing with testosterone for the same receptor. Adding exogenous testosterone in this setting is essentially raising the level of substrate against a competitive blockade. Some effect may come through, but you’d expect a blunted response, and you’d potentially have to push the dose higher to overcome the block, which raises the risk of the very androgenic side effects you’re trying to suppress on the skin.

No randomized trial has directly evaluated the efficacy of systemic testosterone therapy in women concurrently on dermatologic-dose spironolactone. The reverse experiment — using spironolactone to suppress testosterone activity in transgender feminizing hormone therapy — provides clinical proof-of-concept that the antagonism is real and dose-dependent. Multiple dermatology and clinical decision frameworks now explicitly counsel against initiating spironolactone in women already on testosterone therapy. Combining the two doesn’t feel scientifically clean, and in practice, it puts the patient in a position of fighting one prescription against another.

There is, however, indirect data that should inform our thinking. The Cochrane review of 35 trials on testosterone added to postmenopausal hormone therapy confirmed both the benefits women seek — improved sexual function — and the side effects that bring them to my office: increased acne and hirsutism. A 2021 systematic review in the International Journal of Women’s Dermatology found that women on hormone-replacement therapy or androgen blockers are routinely excluded from acne clinical trials. The population this article is actually about is structurally underrepresented in the evidence we have. The knowledge gap isn’t an accident. It’s a design choice we need to correct.

Replenishing hormones locally and reducing the spironolactone dose, however, could be of great benefit. And of course, as with so many clinical questions in women’s hormone health, we don’t have good data either way.

Screen for low androgen symptoms before you start spironolactone

This is the part I want to say loudly to my dermatology colleagues: we should be screening women for symptoms of low androgen activity before we hand them a prescription for an antiandrogen.

Not necessarily checking levels in every patient — the serum testosterone assays in the female range are imprecise, and the correlation between level and symptom is loose. But asking. Five minutes of intake questions about libido, arousal, energy, motivation, mood, vaginal symptoms, and sexual function. If a woman is already symptomatic for low androgen activity in her 40s, putting her on spironolactone is a different decision than putting her on it at 28 with PMOS-driven acne (polyendocrine metabolic ovarian syndrome — the new global consensus name for what we’ve called PCOS for decades).

This screening costs nothing. It changes what we’re treating. And it lets the patient consent to the trade-off with full information instead of finding out six months later that she’s flatter, drier, and less interested in her partner. And she’s upset, rightfully so, because nobody warned her of this possibility.

It also helps explain why the women walking into our offices, saying what else you got, doc are doing so. Many of them have already done this calculus on their own. They are not anti-medication. They are anti-trade-off; no one disclosed.

The case that breaks the protocol

Here is the scenario that makes the personalization argument concrete.

A woman comes to me on testosterone therapy, optimized for her symptoms. Her energy is good, libido is restored, and mood is stable. But she’s developing hormonal acne along her jaw, some new chin hairs, and her part looks wider than it did a year ago. The protocol-medicine reflex would be to add spironolactone.

I won’t do that as my first move. My first move is to check her testosterone levels and confirm she’s still within the female physiologic range. This is a time when testosterone level testing is warranted and useful. If she’s running supraphysiologic, the answer is to adjust her testosterone dose, not add a blocker on top.

If her levels are physiologic and she’s still developing androgenic skin and hair changes — which can absolutely happen in genetically susceptible women even at appropriate doses — then I have to have a real conversation with her. Spironolactone may help her skin and hair. It may also blunt the benefits she’s getting from testosterone therapy. Two prescriptions are now fighting each other inside her body, and the question is which symptoms she most wants resolved.

That conversation isn’t in any algorithm. It depends on her priorities. Some women will say I will take the acne over losing my libido again, I am never going back to how I felt. Others will say I can’t stand looking in the mirror, I’d rather adjust the testosterone down and accept some compromise. Both answers are correct. Neither is something I can decide for her.

There are many other effective treatments for acne, hair loss, and hirsutism that leave the androgens and androgen receptors alone. And even though treating hormonal skin conditions via nonhormonal modalities feels imprecise, it may help women feel more like themselves.

Why protocol medicine fails women

Every medication has trade-offs. Spironolactone helps skin and hair by blocking androgen activity. But blocking androgen activity has costs that show up everywhere from the bedroom to the boardroom. Testosterone therapy restores libido and energy and bone health — and can drive hormonal acne and unwanted hair in susceptible women. Vaginal estrogen helps GSM but doesn’t address the androgen contribution. Each tool is doing real work and producing real downstream effects.

The mistake is to treat each symptom in isolation. To send the acne patient to the dermatologist, the libido patient to the gynecologist, the fatigue patient to the primary care doc, and the vaginal symptoms patient to the urologist, each writing their own prescription without ever zooming out to look at the whole woman.

A 45-year-old patient is not a collection of organs each demanding their own specialist. She has one hormonal system, one set of priorities, one body that has to live with the cumulative effect of every prescription we hand her.

That requires asking. It requires time. It requires admitting we don’t have clean data on many of these combinations and that we’re making judgment calls. And it requires the patient to be part of the decision in a way that protocol medicine simply doesn’t allow.

The women showing up in my office, saying what else you got, doc are not the problem. They are the signal. They are telling us that the old playbook — the SAFA-validated, FASCE-confirmed, decades-deep evidence base on spironolactone — is necessary but not sufficient. We need to be able to hold two things at once: that spironolactone is a powerful, effective drug for the right patient, and that “the right patient” is a more complicated determination than we have been treating it as.

Spironolactone is a good drug. I prescribe it. I will keep prescribing it. But I will not prescribe it without asking the questions first — and I think it’s time we held the whole field to that standard.