Notes on Estradiol and Testosterone Use in Women

Estradiol and the move to estrogen blockade

  • Estradiol levels cited as being called “high” in some studies: an estradiol level of 3030 (units not specified in transcript) was labeled elevated, while normal men have levels around 7575. This is used to illustrate how the movement to block estrogen (via aromatase inhibitors) began, largAely because bodybuilders sought to block formation of estradiol to raise endogenous testosterone.

  • Key idea: blocking aromatase to reduce estradiol increases testosterone activity, influencing body composition and performance signals.

Testosterone in females: recognition, off-label use, and documentation

  • Testosterone is not FDA-approved for women, but it is not prohibited to prescribe off-label when clinically appropriate.

  • When prescribing in this context, you should document in the chart: “the patient is requesting testosterone to improve symptoms and signs of a deficiency, and I am prescribing testosterone for off-label use.”

  • Claimed benefits in women include improvements in:

    • Overall well-being

    • Strength, energy, endurance

    • Body composition, fat mass reduction, muscle mass

    • Fat burning, metabolism

    • Bone density

    • Sexual function

  • Anecdotal vignette: an elderly patient (in their 60s) brought her mother (age ~85) for treatment; the patient reported feeling better on hormones, but then described a side effect:

    • Breast tenderness

    • Difficulty sleeping

    • She reported being horny, which prompted discussion about management of GSM (genitourinary syndrome of menopause) in an older patient.

  • GSM and female sexual health: terminology evolution from vaginal atrophy to genitourinary syndrome of menopause; testosterone in the genital area can improve clitoral sensitivity and orgasmic ability.

  • Benefits noted include Mayo Clinic findings: testosterone may improve muscle mass by about 6 ext{%} and reduce fat mass by 4 ext{-}6 ext{%}.

  • Cardiovascular notes:

    • Estradiol (oral) is standard for cardiovascular protection, but testosterone also has a beneficial effect by stimulating the androgen receptor and reducing visceral fat, which relates to insulin resistance and CV risk.

    • Overall, testosterone is framed as protective for cardiovascular health through body composition and metabolic effects.

  • Ethical and practical point: testosterone is not a male hormone alone; it has important roles in women too. Some patients report physicians discouraging use due to bias or misperceptions about risks.

  • Skin effects: literature documents beneficial effects of estrogen and testosterone on the skin, including reductions in visceral fat, subcutaneous fat, and dermal fat deposition.

Formulations, dosing, and administration in women

  • Cream formulations discussed:

    • Men: 20% testosterone cream (higher potency)

    • Women: 2% testosterone cream (20 mg/g)

    • The base is a cream base; often referred to as “cream base” (previously “hormone base”).

  • Standard prescription example for vaginal application:

    • Micronized testosterone cream, 2 ext{%}, base: cream base

    • Dose: one pea-sized amount equals rac14extg=0.25extgrac{1}{4} ext{ g} = 0.25 ext{ g} applied to the external labia, QHSQHS (nightly)

    • Calculated testosterone delivery from a 2% cream with 0.25 g dose:
      0.25 extg×0.02=0.005 extg=5 extmg0.25\, ext{g} \times 0.02 = 0.005\, ext{g} = 5\, ext{mg}

  • Absorption considerations:

    • Vaginal/labial mucosa provides superior absorption; absorption from mucosa is preferable for achieving target levels.

    • If a patient cannot apply to the labia, the next best area is the upper inner arm (thin skin, low hair follicles) for dermal absorption.

    • To match labial absorption levels when using the upper inner arm, a higher concentration is required:

    • 2% cream applied to the labia can achieve a certain level; to achieve similar systemic levels in arm, use 4% cream.

    • Dose example: 0.25 extg×0.04=0.01 extg=10 extmg0.25\, ext{g} \times 0.04 = 0.01\, ext{g} = 10\, ext{mg} per day if using 4% cream on the upper inner arm.

  • Practical dosing guidance:

    • If using labial application: start with 2% cream, 0.25 g, once daily at night (QHS).

    • If patient is noncompliant with labial application: use 4% cream on the upper inner arm, 0.25 g once daily.

    • If the patient already has 2% cream on hand and wants to continue, you can increase the amount by doubling dose on the arm (e.g., 0.25 g to 0.5 g) to maintain systemic exposure.

    • For women who are forgetful: set reminders; the speaker suggests placing the cream near the toothbrush as a cue to apply before bed.

  • Alternatives and considerations:

    • If skin sensitivity to the base occurs, use Elage cream base (hypoallergenic).

    • The clinician warns that male staff may not understand vaginal application, so involve female staff when discussing GSM and labial administration.

  • Practical notes on administration:

    • The same base and cream logic used in men applies to women, but absorption and compliance differ; vaginal absorption yields higher levels, so dosing differs.

    • The clinician emphasizes simple, consistent application and patient education to improve adherence.

  • Patient optimization tips:

    • Some patients prefer evening application; others are flexible.

    • If labial application is not acceptable, shift to upper inner arm with higher concentration; ensure the patient understands the rationale and dosing changes.

Side effects and management in women; adjunct strategies

  • Side effects in women are more common than in men, with acne and hirsutism being the typical concerns.

    • If acne/hirsutism develops: reduce the testosterone dose or pause until side effects resolve, then restart at a lower dose (often half-dose or alternate days).

  • Spironolactone as a countermeasure for acne/hirsutism:

    • Typical dermatologic dose used to prevent acne/hirsutism with testosterone: 100 extmg100\, ext{mg} per day.

    • Time to effectiveness: about 2ext−3 months2 ext{-}3\text{ months}.

    • If acne/hirsutism occurs, stopping testosterone briefly, then restarting at a reduced dose together with spironolactone is suggested.

  • PCOS considerations (pathophysiology and management):

    • PCOS is driven by insulin resistance; acne/hirsutism in PCOS is a red flag for insulin resistance.

    • Treatments include metformin and spironolactone; thyroid hormone may be used to reduce visceral fat and improve insulin sensitivity.

    • The combination of estradiol and thyroid hormone may help raise SHBG, which lowers free testosterone and reduces acne/hirsutism.

  • SHBG and testosterone physiology in menopausal women:

    • Insulin resistance lowers SHBG; higher SHBG binds free testosterone, reducing androgenic side effects.

    • Oral estradiol raises SHBG (transdermal estradiol does not affect SHBG).

    • Raising SHBG through oral estradiol helps mitigate acne/hirsutism by decreasing free testosterone.

  • Testosterone indications in women: symptoms-based therapy rather than strict lab thresholds

    • If a woman has symptoms of low testosterone (fatigue, reduced energy, reduced sexual function), testosterone may be used off-label.

    • Guidelines for women generally advise against routine measurement of testosterone levels to guide therapy; there is a tension between symptom-based therapy and laboratory monitoring.

    • Some sources (as cited in the transcript) suggest that total testosterone levels > 300300 may be associated with symptom improvement in some women, though this is not universally agreed and is contrasted with normal female ranges of roughly 20extto7520 ext{ to }75.

  • Dosing philosophy and monitoring in women:

    • In women, decisions often rely on symptoms rather than numerical targets; levels do not always correlate with clinical response.

    • Some patients may require very high total testosterone levels (the speaker mentions levels up to 18001800 in a cited individual) to achieve symptom relief, but this must be individualized and monitored for side effects.

  • Clinical caution and contraindications:

    • Contraindications include pregnancy or plan to become pregnant.

    • Some patients may be resistant to testosterone therapy due to fear of side-effects (e.g., facial hair, aggression); patient education is important.

  • Summary observation on breast cancer prevention

    • The speaker suggests testosterone may have a protective role against breast cancer in some contexts; this view reflects a perspective from the speaker and is not presented as universal consensus.

Pathophysiology connections: insulin resistance, SHBG, and estradiol

  • Insulin resistance drives PCOS; elevated insulin reduces SHBG, increasing free testosterone and risk of acne/hirsutism.

  • Increasing SHBG reduces free testosterone and mitigates androgenic symptoms; oral estradiol is a lever to raise SHBG in menopausal women, whereas transdermal estradiol does not affect SHBG.

  • Visceral fat and metabolic risk:

    • Testosterone reduces visceral fat and, through androgen receptor signaling, can improve insulin sensitivity and metabolic risk.

    • Thyroid hormone can further reduce visceral fat and improve insulin resistance, contributing to better metabolic health.

  • Treatment strategy in GSM and menopause:

    • The goal is to improve genitourinary symptoms (e.g., vaginal dryness, leakage with coughing) and sexual function, while managing androgenic side effects.

    • The combination of estrogen (to raise SHBG) and targeted testosterone therapy (with careful monitoring) can provide symptom relief and functional gains without excessive androgenic adverse effects.

Laboratory considerations and clinical guidelines discussed

  • For women, the lecture emphasizes symptom-guided treatment over routine lab-directed therapy:

    • “Total testosterone level” thresholds are discussed as potential guides in some literature, but the overarching guideline in this talk is not to rely on levels alone for therapy in women; focus on symptoms.

    • When testing is done, values such as normal female ranges (20$
      to 75)arecited,withasuggestionthatatotaltestosteronearound) are cited, with a suggestion that a total testosterone around300maybeassociatedwithsymptomreliefinsomecases,thoughthisisnotuniversallyaccepted.</p></li></ul></li><li><p>Generalclinicalpoint:beawareofthepatient’spregnancystatus,patientpreferences,andthepotentialforsideeffects;adjusttherapyaccordingly.</p></li></ul><h4id="0ab9b316−bb3b−4886−8a9c−4ba9fe5531f1"data−toc−id="0ab9b316−bb3b−4886−8a9c−4ba9fe5531f1"collapsed="false"seolevelmigrated="true">Practicaltakeawaysforclinicians</h4><ul><li><p>Addresspatientrequestsfortestosteroneinwomenwithcleardocumentationofoff−labeluseandsymptom−drivengoals.</p></li><li><p>Considervaginal/labialadministrationtomaximizelocalabsorptionandsymptomrelief,withcarefulpatienteducationaboutapplicationandadherence.</p></li><li><p>Ifadherenceisachallenge,consideralternativesites(upperinnerarm)andhigherconcentrationtoachievesimilarsystemicexposure,whileexplainingtherationaletothepatient.</p></li><li><p>Beproactiveinmanagingsideeffectswithdoseadjustments,stoppingtherapyifneeded,andaddingadjuncttherapies(e.g.,spironolactoneforacne/hirsutism).</p></li><li><p>Usespironolactone(e.g.,100mg/day)foracne/hirsutismwhenthereisandrogenexcessduetotestosteronetherapy;expectalagtimeofseveralweekstomonthsforfulleffect.</p></li><li><p>Consideraddressingunderlyingmetabolicfactors(insulinresistance,visceralfat)withmetforminandthyroidhormoneasappropriate,especiallyinPCOSorpostmenopausalpatientswithinsulinresistance.</p></li><li><p>EducatepatientsaboutGSM,sexualfunction,andskinhealthbenefitsfromhormonetherapy,whileaddressingmythsandmisconceptionsabouttestosteroneinwomen.</p></li><li><p>Rememberpracticalcommunicationdynamicswithinthecareteam:involvefemalestaffwhendiscussingfemalegenital−areatreatmentstoensurepatientcomfortandcomprehension.</p></li><li><p>Alwaysassesspregnancystatusandcontraindicationsbeforeinitiatinganytestosterone−basedtherapyinwomen.</p></li></ul><h4id="0d7686e6−f815−4292−96ec−7db249a677bc"data−toc−id="0d7686e6−f815−4292−96ec−7db249a677bc"collapsed="false"seolevelmigrated="true">Quickreference:keynumericalandconceptualanchors</h4><ul><li><p>Estradiollevelsmentioned:may be associated with symptom relief in some cases, though this is not universally accepted.</p></li></ul></li><li><p>General clinical point: be aware of the patient’s pregnancy status, patient preferences, and the potential for side effects; adjust therapy accordingly.</p></li></ul><h4 id="0ab9b316-bb3b-4886-8a9c-4ba9fe5531f1" data-toc-id="0ab9b316-bb3b-4886-8a9c-4ba9fe5531f1" collapsed="false" seolevelmigrated="true">Practical takeaways for clinicians</h4><ul><li><p>Address patient requests for testosterone in women with clear documentation of off-label use and symptom-driven goals.</p></li><li><p>Consider vaginal/labial administration to maximize local absorption and symptom relief, with careful patient education about application and adherence.</p></li><li><p>If adherence is a challenge, consider alternative sites (upper inner arm) and higher concentration to achieve similar systemic exposure, while explaining the rationale to the patient.</p></li><li><p>Be proactive in managing side effects with dose adjustments, stopping therapy if needed, and adding adjunct therapies (e.g., spironolactone for acne/hirsutism).</p></li><li><p>Use spironolactone (e.g., 100 mg/day) for acne/hirsutism when there is androgen excess due to testosterone therapy; expect a lag time of several weeks to months for full effect.</p></li><li><p>Consider addressing underlying metabolic factors (insulin resistance, visceral fat) with metformin and thyroid hormone as appropriate, especially in PCOS or postmenopausal patients with insulin resistance.</p></li><li><p>Educate patients about GSM, sexual function, and skin health benefits from hormone therapy, while addressing myths and misconceptions about testosterone in women.</p></li><li><p>Remember practical communication dynamics within the care team: involve female staff when discussing female genital-area treatments to ensure patient comfort and comprehension.</p></li><li><p>Always assess pregnancy status and contraindications before initiating any testosterone-based therapy in women.</p></li></ul><h4 id="0d7686e6-f815-4292-96ec-7db249a677bc" data-toc-id="0d7686e6-f815-4292-96ec-7db249a677bc" collapsed="false" seolevelmigrated="true">Quick reference: key numerical and conceptual anchors</h4><ul><li><p>Estradiol levels mentioned:30(claimedhigh)vsnormalmen(claimed high) vs normal men75.</p></li><li><p>Testosteroneeffectsinwomen:improvementsinwell−being,strength,energy,endurance,bodycomposition,bonedensity,sexualfunction.</p></li><li><p>Mayoarticlecited:musclemass+.</p></li><li><p>Testosterone effects in women: improvements in well-being, strength, energy, endurance, body composition, bone density, sexual function.</p></li><li><p>Mayo article cited: muscle mass +6\%;fatmass−; fat mass −4\%$ to −6%6\% with testosterone.

    • Cream concentrations and dosing:

      • Men: 20%20\% testosterone cream; Women: 2%2\% cream (20 mg/g).

      • Labial application: 0.25 g0.25\text{ g} (one pea-sized amount) QHS → 0.25 g×0.02=0.005 g=5 mg0.25\text{ g} \times 0.02 = 0.005\text{ g} = 5\text{ mg} per dose.

      • If using upper inner arm: 0.25 g×0.04=0.01 g=10 mg0.25\text{ g} \times 0.04 = 0.01\text{ g} = 10\text{ mg} per dose; equivalence requires adjusting concentration.

    • Practical dosing quotes:

      • Labial: 2% cream, 0.25 g, QHS; switch to 4% cream on arm at 0.25 g if labial application is not feasible.

      • If patient already has 2% cream and cannot apply labially, may increase dose on arm to maintain exposure (e.g., 0.5 g doses).

    • Time to effect for spironolactone in acne/hirsutism: 2ext−3 months2 ext{-}3\text{ months}.

    • Indications for testosterone treatment in women: symptoms of low testosterone (fatigue, reduced energy, reduced sexual function, etc.).

    • Total testosterone thresholds mentioned: around 300300 (some sources); normal female range 20extto7520 ext{ to }75; very high reported examples (e.g., up to 18001800) cited in the text.

    • Key terms:

      • GSM: genitourinary syndrome of menopause

      • SHBG: sex hormone-binding globulin

      • PCOS: polycystic ovary syndrome

      • Metformin and thyroid hormone as metabolic modifiers

    Summary note

    • The transcript presents a clinician’s perspective on estradiol and testosterone use in women, emphasizing symptom-driven, off-label testosterone therapy with careful dosing (labial vs arm), mindful of adherence and side effects (acne/hirsutism).

    • It highlights the importance of GSM management, SHBG modulation (via oral estradiol), and addressing insulin resistance in PCOS or menopausal patients.

    • The clinician argues for a broader recognition of testosterone’s benefits in women, including skin health and cardiovascular considerations, while acknowledging biases and the need for careful monitoring and patient education.