Chapter 22 · Greater Boston Urology · Massachusetts
Hormone Replacement Therapy: Men & Women
Greater Boston Urology cares for both men and women, and hormone therapy is a high-value part of that care. This chapter covers testosterone therapy in men and menopausal hormone therapy in women — including the local vaginal estrogen that is so useful…
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Greater Boston Urology
cares for both men and women, and hormone therapy is a high-value
part of that care. This chapter covers testosterone therapy in men
and menopausal hormone therapy in women — including the local
vaginal estrogen that is so useful for the urinary symptoms we treat.
As always, diagnose before you treat, and monitor deliberately.
22.1 Testosterone therapy in men
Diagnosis first — and get this right
Require
BOTH symptoms and biochemistry: consistent symptoms (low libido,
fatigue, ED, loss of morning erections, reduced motivation, loss of
muscle mass, depressed mood) PLUS at least TWO low early-morning
(before 10 a.m.) total testosterone levels — commonly below ~300
ng/dL. Testosterone has a marked diurnal rhythm; an afternoon level
is meaningless.
Use free
testosterone when SHBG is abnormal or the total is borderline —
obesity and diabetes lower SHBG (making total T look falsely low),
while aging and liver disease raise it.
Find the
cause: check LH/FSH (high = primary testicular failure; low or
inappropriately normal = secondary/central), prolactin (a
prolactinoma is treatable and must not be missed), and consider iron
studies (hemochromatosis). Evaluate for reversible contributors:
obesity, obstructive sleep apnea, opioids, alcohol, and
glucocorticoids. Treating the OSA sometimes fixes the testosterone.
Baseline
before starting: hematocrit and PSA, and an explicit fertility
conversation.
Formulations — our practice preference order
We rank
formulations by how physiologic and easy they are, not just by
potency:
our practice rank
Formulation
Why / notes
1st choice
Topical gel (daily transdermal)
Easiest to use and the most physiologic — it mimics the normal
daily testosterone rhythm and titrates smoothly. Counsel on
transference to partners/children (wash hands, cover the site,
avoid skin-to-skin contact until absorbed).
2nd choice
Pellets (SC, every 3–6 months)
Steady levels and very convenient — no daily dosing and
excellent adherence. Requires a minor in-office insertion;
extrusion and infection are uncommon risks.
Last choice
Injections (IM/SC cypionate or enanthate)
Effective and inexpensive, but produces a roller-coaster of
testosterone levels — supraphysiologic peaks and low troughs
that swing energy, mood, and libido, and drive erythrocytosis. We
use them last for that reason.
our practice generally avoids oral testosterone because of high cost and
poor insurance coverage — not a value proposition for most
patients.
Manage
estrogen with anastrozole when needed: some men aromatize
testosterone to estradiol, causing gynecomastia, water retention,
nipple tenderness, or mood changes. A low-dose aromatase inhibitor
(anastrozole) reduces estrogen and is a useful adjunct — check
estradiol and avoid over-suppression, because too-low estradiol
harms bone density, libido, and lipids. Do not use it reflexively in
every man; use it when the estradiol and the symptoms justify it.
Monitoring and safety
What
When
Action threshold
Symptoms
3, 6, 12 months, then annually
If no symptomatic benefit after an adequate trial at a
therapeutic level, STOP — do not continue a drug that is not
working
Testosterone level
3, 6, 12 months, then annually (timing depends on formulation)
Target mid-normal range. Do not chase supraphysiologic levels
Hematocrit
Baseline, 3–6 months, then annually
Hold or reduce the dose if > ~54% (erythrocytosis raises
thrombotic risk). Therapeutic phlebotomy if needed. Most common
with injections
PSA
Baseline, then per prostate-cancer screening norms
Evaluate a confirmed rise BEFORE continuing (PSA/MRI pathway —
Chapter 8; we do not rely on the DRE)
Contraindications/cautions:
untreated prostate or breast cancer; an unevaluated elevated
PSA; hematocrit already elevated; untreated severe obstructive sleep
apnea; uncontrolled heart failure; a recent cardiovascular event
(within ~3–6 months); and — the one most often violated — men
actively seeking fertility.
Testosterone counseling pearls
Contemporary
cardiovascular-safety data (the TRAVERSE trial) did not show an
increased rate of major adverse cardiac events with appropriately
prescribed testosterone in hypogonadal men with cardiovascular
risk — but individualize and monitor, and note there were
signals for atrial fibrillation and pulmonary embolism.
Do NOT prescribe
testosterone to a man trying to conceive; it suppresses
spermatogenesis and can cause reversible (occasionally prolonged)
infertility. Use enclomiphene, clomiphene, or hCG instead.
Testosterone is not a
wellness supplement. Diagnose properly, treat the diagnosis, and
monitor — or do not start.
A confirmed rising PSA on therapy warrants evaluation
before continuing.
22.2 Menopausal hormone therapy (women)
Menopausal
hormone therapy (MHT) treats bothersome vasomotor symptoms and
protects bone. Highly relevant to urology, local vaginal estrogen
relieves the genitourinary syndrome of menopause and reduces
recurrent UTIs — and it is a completely different risk conversation
from systemic therapy.
Systemic MHT
Indications:
bothersome vasomotor symptoms (hot flashes, night sweats) and
prevention of bone loss in appropriate candidates.
Estrogen
± progestogen: add a progestogen for any woman with an INTACT
UTERUS to protect the endometrium from unopposed-estrogen
hyperplasia and carcinoma. Estrogen alone if she has had a
hysterectomy.
The
timing principle: the benefit-risk balance is most favorable
when MHT is started in symptomatic women under age 60 OR within 10
years of menopause. Starting it late (a decade or more out) is where
the cardiovascular harm signal in the WHI came from — the drug did
not change; the population did.
Route
matters: TRANSDERMAL estrogen avoids first-pass hepatic
metabolism and carries a lower VTE risk than oral — prefer it in
women with any thrombotic risk.
Risks/contraindications:
venous thromboembolism, stroke, and — with long-term combined
therapy — breast cancer. Avoid with a hormone-sensitive cancer,
unexplained vaginal bleeding, active VTE or cardiovascular disease,
or significant liver disease.
Local vaginal estrogen — the urology workhorse
Use it
for: vaginal dryness and dyspareunia, and the urinary symptoms
of menopause — recurrent UTIs, urgency, frequency, and dysuria
(cross-reference Chapters 6 and 15). It is one of the highest-yield
tools in this book.
Safety:
minimal systemic absorption; it does NOT require a progestogen,
and the FDA has REMOVED the boxed warning from low-dose vaginal
estrogen. Appropriate for long-term use in most women, including
many with a breast-cancer history (coordinate with their oncologist
— aromatase-inhibitor patients need individual discussion).
Alternatives:
vaginal DHEA (prasterone) and oral ospemifene for genitourinary
symptoms.
Testosterone in women
The single
evidence-based indication is hypoactive sexual desire disorder in
postmenopausal women — low-dose, off-label (there is no
FDA-approved female formulation), titrated to female physiologic
levels, with monitoring for acne, hirsutism, and voice change. Avoid
supraphysiologic dosing and compounded pellets, which frequently
overshoot.
Women's hormone pearls
For a woman whose main
problem is recurrent UTIs or urinary urgency after menopause,
LOCAL VAGINAL ESTROGEN is one of the highest-yield, lowest-risk
tools you have. Prescribe it far more often than you think you
should.
Systemic and local estrogen
are entirely different conversations — local vaginal estrogen
is NOT systemic HRT and carries a very different risk profile. Do
not let a patient (or another clinician) conflate them and refuse
a safe, effective therapy.
Non-hormonal options for vasomotor symptoms exist for
women who cannot take estrogen: SSRIs/SNRIs, gabapentin, and
fezolinetant.
Clinical Pathway
Click any node to expand
Hormone therapy at Greater Boston Urology runs on two separate tracks — testosterone in men and menopausal hormone therapy in women — plus the local vaginal estrogen that is one of the highest-yield tools in urology. Diagnose before you treat, and monitor deliberately.
Symptoms AND biochemistry, a cause hunt, then our practice formulation preference order — and monitoring that is willing to stop the drug.
Select a box to open its teaching details.
Consistent symptoms
Low libido
Fatigue
Erectile dysfunction
Loss of morning erections
Reduced motivation
Loss of muscle mass
Depressed mood
Frame it correctly
Testosterone is not a wellness supplement. Diagnose properly, treat the diagnosis, and monitor — or do not start.
Ch 22.1 — diagnosis first
The threshold
At least two low early-morning (before 10 a.m.) total testosterone levels
Commonly below ~300 ng/dL
PLUS consistent symptoms — you need both halves
Why the timing
Testosterone has a marked diurnal rhythm. An afternoon level tells you nothing and will mislead you in both directions.
Pitfalls
Treating on a single level
Treating on an afternoon draw
Treating a number in a man with no symptoms
Ch 22.1 — diagnosis first
What moves SHBG
Obesity and diabetes LOWER SHBG — making the total T look falsely low
Aging and liver disease RAISE SHBG — which can mask a truly low free T
When to order it
Abnormal or suspected-abnormal SHBG
A borderline total testosterone
Ch 22.1 — diagnosis first
Orders
LH/FSH — high = primary testicular failure; low or inappropriately normal = secondary/central
Prolactin — a prolactinoma is treatable and must not be missed
Consider iron studies (hemochromatosis)
Reversible contributors to hunt for
Obesity
Obstructive sleep apnea — treating the OSA sometimes fixes the testosterone
Opioids
Alcohol
Glucocorticoids
Pitfalls
Replacing testosterone and never checking a prolactin — a missed prolactinoma
Ignoring a reversible cause that would have fixed the problem without a lifelong drug
Ch 22.1 — diagnosis first
Baseline before starting
Hematocrit
PSA
An explicit fertility conversation — documented
Ch 22.1 — diagnosis first
Is he trying to conceive — now or in the foreseeable future?
Why
Exogenous testosterone suppresses spermatogenesis and can cause reversible — occasionally prolonged — infertility.
Use instead
Enclomiphene
Clomiphene
hCG
Pitfalls
Starting a young man on gel without ever asking about fertility plans
Ch 22.1 — counseling pearls
Before you proceed
Confirm no untreated prostate or breast cancer
Confirm the PSA has been evaluated if elevated
Confirm hematocrit is not already elevated
Ch 22.1 — contraindications/cautions
Choose the formulation — our practice preference order ranks by how physiologic and easy it is, not just potency
Local policy
Our protocol
our practice 1st choice. Daily transdermal gel mimics the normal daily testosterone rhythm and titrates smoothly
Counsel on transference
Wash hands after application
Cover the application site
Avoid skin-to-skin contact with partners and children until absorbed
Ch 22.1 — formulations
Local policy
Our protocol
our practice 2nd choice. Pellets SC every 3–6 months — no daily dosing and excellent adherence
Trade-offs
Requires a minor in-office insertion
Extrusion and infection are uncommon risks
Ch 22.1 — formulations
Our protocol
our practice last choice. Cypionate or enanthate produce supraphysiologic peaks and low troughs
Why last
Swings in energy, mood, and libido track the peaks and troughs
Drives erythrocytosis — the hematocrit problem is most common with injections
Ch 22.1 — formulations
Our protocol
our practice generally avoids oral testosterone (e.g., Kyzatrex, oral testosterone undecanoate)
Reason: high cost and poor insurance coverage
Ch 22.1 — formulations
Symptoms that suggest excess aromatization
Gynecomastia
Water retention
Nipple tenderness
Mood changes
How to use it
A low-dose aromatase inhibitor (anastrozole) reduces estrogen and is a useful adjunct
Check estradiol and avoid over-suppression
Pitfalls
Do not use it reflexively in every man
Too-low estradiol harms bone density, libido, and lipids
Ch 22.1 — formulations
Monitoring schedule
Symptoms — 3, 6, 12 months, then annually
Testosterone level — 3, 6, 12 months, then annually (timing depends on formulation); target mid-normal range, do not chase supraphysiologic levels
Hematocrit — baseline, 3–6 months, then annually
PSA — baseline, then per prostate-cancer screening norms
Action thresholds
Hematocrit > ~54% → hold or reduce the dose; therapeutic phlebotomy if needed (erythrocytosis raises thrombotic risk)
A confirmed PSA rise → evaluate before continuing, via the PSA/MRI pathway (Chapter 8) — we do not rely on the DRE
Ch 22.1 — monitoring and safety
The rule
After an adequate trial at a therapeutic level with no symptomatic benefit, stop the testosterone. Continuing exposes the patient to erythrocytosis, fertility suppression, and cost for nothing.
Ch 22.1 — monitoring and safety
Contraindications / cautions
Untreated prostate or breast cancer
An unevaluated elevated PSA
Hematocrit already elevated
Untreated severe obstructive sleep apnea
Uncontrolled heart failure
A recent cardiovascular event (within ~3–6 months)
Men actively seeking fertility — the one most often violated
Cardiovascular counseling
The TRAVERSE trial did not show an increased rate of major adverse cardiac events with appropriately prescribed testosterone in hypogonadal men with cardiovascular risk — but individualize and monitor, and note there were signals for atrial fibrillation and pulmonary embolism.
Ch 22.1 — counseling pearls
Menopausal hormone therapy for bothersome vasomotor symptoms and bone protection — where timing and route do most of the risk work.
Select a box to open its teaching details.
Indications for systemic MHT
Bothersome vasomotor symptoms (hot flashes, night sweats)
Prevention of bone loss in appropriate candidates
Ch 22.2 — systemic MHT
The favorable window
Symptomatic women under age 60, OR
Within 10 years of menopause
Why it matters
Starting MHT late — a decade or more out from menopause — is where the cardiovascular harm signal in the WHI came from. Understanding this lets you have an accurate conversation instead of a fearful one.
Ch 22.2 — systemic MHT
Does she have an intact uterus?
Why
A progestogen is added for any woman with an intact uterus to protect the endometrium from unopposed-estrogen hyperplasia and carcinoma.
Pitfalls
Prescribing estrogen alone to a woman who still has her uterus
Ch 22.2 — systemic MHT
Regimen
Estrogen alone if she has had a hysterectomy
Ch 22.2 — systemic MHT
Why transdermal
Transdermal estrogen avoids first-pass hepatic metabolism and carries a lower VTE risk than oral. Prefer it in women with any thrombotic risk.
Ch 22.2 — systemic MHT
Avoid systemic MHT with
A hormone-sensitive cancer
Unexplained vaginal bleeding
Active VTE or cardiovascular disease
Significant liver disease
Risks to disclose
Venous thromboembolism
Stroke
Breast cancer — with long-term combined therapy
Ch 22.2 — systemic MHT
Non-hormonal options for vasomotor symptoms
SSRIs / SNRIs
Gabapentin
Fezolinetant
Ch 22.2 — women's hormone pearls
Pitfalls
Systemic and local estrogen are entirely different conversations — local vaginal estrogen is NOT systemic HRT and carries a very different risk profile
Do not let a patient — or another clinician — conflate them and refuse a safe, effective therapy
Where to go next
If her dominant problem is urinary or genitourinary, work the Local vaginal estrogen track instead.
Ch 22.2 — women's hormone pearls
The urology workhorse — genitourinary syndrome of menopause, recurrent UTIs, and the urinary symptoms we see every day.
Select a box to open its teaching details.
Use local vaginal estrogen for
Vaginal dryness and dyspareunia
Recurrent UTIs
Urgency and frequency
Dysuria
Cross-reference
See Chapters 6 and 15 for the UTI and female-urology pathways this feeds.
Ch 22.2 — local vaginal estrogen
Local policy
Our position
For a woman whose main problem is recurrent UTIs or urinary urgency after menopause, local vaginal estrogen is one of the highest-yield, lowest-risk tools you have
Prescribe it far more often than you think you should
Ch 22.2 — women's hormone pearls
What to tell her
Minimal systemic absorption
It does NOT require a progestogen
The FDA has REMOVED the boxed warning from low-dose vaginal estrogen
Appropriate for long-term use in most women
Ch 22.2 — local vaginal estrogen
How to handle it
Appropriate for many women with a breast-cancer history — coordinate with their oncologist
Aromatase-inhibitor patients need an individual discussion
Pitfalls
Denying a safe, effective therapy because someone confused it with systemic HRT
Ch 22.2 — local vaginal estrogen
Alternatives
Vaginal DHEA (prasterone)
Oral ospemifene
Ch 22.2 — local vaginal estrogen
How it is used
Low-dose and off-label — there is no FDA-approved female formulation
Titrated to female physiologic levels
Monitor for acne, hirsutism, and voice change
Pitfalls
Avoid supraphysiologic dosing
Avoid compounded pellets, which frequently overshoot
Ch 22.2 — testosterone in women
What you are looking for
Fewer recurrent UTIs
Less urgency, frequency, and dysuria
Relief of dryness and dyspareunia
Pitfalls
Stopping it after a short trial — this is appropriate for long-term use in most women