TUESDAy, MARCH 3 , 2020. THE WASHINGTON POST eZ ee E5
Alternative therapies
While nothing is as effective as hormones,
experts say, there are other treatment options
for women who cannot take them. the food and
drug administration has approved a low-dose
form of the antidepressant paroxetine (Brisdelle)
for menopause symptoms, and it can take the
edge off hot flashes, stephanie faubion, medical
director of the north american Menopause
society, says. some doctors also prescribe other
low-dose antidepressants, although these come
with risks that should be discussed ahead of
time.
faubion and her colleagues recently completed a
study suggesting that oxybutinin, a nonhormonal
drug for treating overactive bladders, reduced
the frequency and severity of hot flashes
compared with a placebo. if the finding is
confirmed, it could offer another alternative.
there are also promising studies underway
testing whether nK3-inhibitors, drugs that target
brain receptors involved in hot flash generation,
can provide another alternative to hormones.
Unfortunately, no lifestyle or herbal remedy has
ever been proven to work, faubion says. But that
is not to say that some women do not swear by
these treatments, because the placebo response
for hot flashes is high.
“if you give women a sugar pill, and tell her it will
help with your hot flashes, it will reduce anxiety
associated with hot flashes and therefore reduce
the hot flashes,” she says.
two behavioral approaches with some evidence
to back them — cognitive behavioral therapy and
hypnosis — probably work by reducing anxiety,
faubion says.
— Christie Aschwandenwas. As was required, he had
shaved his head.
Essential tremor i s a neurolog-
ical disease that can affect the
torso, arms, neck, head or even
voice. medications are used to
attenuate symptoms, but for
many patients, these fail or are
difficult to tolerate.
“I don’t want to take medica-
tions forever,” he said.
A particularity to this disease
is social visibility. Like our pa-
tient, people with essential trem-
or tend t o withdraw f rom s ociety,
feeling s elf-conscious about their
inability t o perform s imple tasks.
Dropping food, drinks or other
objects is quickly noticed by
others.
Slowly but eventually, the dis-
ease robs them of their volition
and poise.
“It’s embarrassing,” he admit-
ted. “It is not the way I want to
live. I can’t write my own name
anymore.”
The dentist had even parted
with his hobbies. Painting, play-
ing guitar and doing handiwork
around the house were further
victims of his disease. His wife,
his right hand in his practice,
Tremor from e1 assisted him however she could
in his retirement, but it wasn’t
the same.
He decided to be treated with
mrI-guided focused ultrasound
surgery.
In t his bloodless s urgery, 1 ,000
transmitters housed in a water-
cooled helmet produce sound
waves, all directed at a single
spot in the brain. Where these
waves merge, they increase the
temperature of the tissue, and
ultimately burn a hole the size of
a sesame seed in the brain.
The neurosurgeon pinned a
metal frame around his head.
New mrI scans performed with
this frame holding his head in
place were aligned to his prior
brain imaging, enabling a com-
puter to precisely navigate his
anatomy in 3-D space.
He lay down on the mrI table,
with his bare scalp to the helmet.
I peered over and asked him how
he was faring.
“I feel fine,” he said, “I’m used
to looking at people upside down
anyway.”
A wall of glass separated him
and the table from us, a team of
his doctors and nurses. We were
in a mission control center, but
with sights on the cerebral, not
the celestial.
our target was a portion of his
left thalamus, which controls his
right side. An omniscient satel-
lite, this dense collection of neu-
rons receives data on sensation
and movement in the right body
and transmits it to the rest of the
brain.Like cartographers, the neuro-
surgeon and neuroradiologist
measured and directed the ini-
tial position of the sound waves.
Here, more than most areas,
the brain’s anatomy is unforgiv-
ing. one false millimeter in the
wrong direction could mean
transient or permanent side ef-
fects such as arm numbness or a
wobbly gait. Each dose of soundapplied t o the brain c an b e tested
first with a lower intensity, to
check for reduced tremor and
these effects, before the intensity
is increased, and the lesion is
made permanent.
This energy was intermittent-
ly applied to the target. With
each application, a neurologist
tested the patient’s right hand
tremor, asking him to trace be-
tween two lines and to draw a
spiral. This millimeter march
progressed for two hours, until
the neurologist tested his tremor
one more time.
“If you had this control, this
exact control for the rest of your
life, would you be happy?” he
asked our patient.
“Extremely happy,” he re-
sponded.
With that, his treatment end-
ed. He was gently helped off the
table. The head frame was re-
moved and his scalp dried. A
nurse gave him a pen and paper
to demonstrate his control. He
signed his name with delight,
grinning at his penmanship.
His wife and son, brimming
with anticipation, were brought
in to see him. Their eyes met the
papers he’d been writing on.
“That is your signature,” sheasked in disbelief. “ You did this?”
In his raw account of his
neurosurgery training, “When
the Air Hits Your Brain,” frank
Vertosick Jr. insists upon know-
ing the patient. “To have the
audacity to cut into a person’s
brain without the slightest clue
of his life, his occupation... I
find that most simply appalling,”
he cautions.
There is no cutting in focused
ultrasound surgery, but Verto-
sick’s words resurfaced in my
mind as I watched a once tremu-
lous dentist enjoy his recaptured
freedom. To this man, itself a
Latin root meaning hand, his
dexterity was his livelihood.
With a steady hand, a first in
years, he signed his name again
for his wife.
Science is still explaining our
patient’s tremor, and why inter-
rupting the circuits in the thala-
mus as we did can treat it. Still,
with such improvements, mrI-
guided focused ultrasound sur-
gery is being investigated for
treating several neurological dis-
eases. In a landmark trial for
one-sided hand tremor, this pro-
cedure r educed symptoms signif-
icantly, and improved patients’
ability to eat, drink, dress them-selves, write, work and socialize.
We were discussing this on a
phone call two months after that
day.
“I’ve been playing guitar, and
I’m going to start painting
again,” he said. “Ninety to 95 per-
cent of my tremor is gone.”
With one set of frequencies
and amplitudes, sound can burn
a hole in the brain, with another,
we hear the strumming of a
guitar.
In neurosurgery, we are used
to performing heroics. Within
narrow time scales, we try to
stave off human mortality. In
cases like these, we hope to
provide another, equally impor-
tant aspect to life — quality.
We try to look for context
when we meet patients. We ask
about likes, hobbies, occupa-
tions. As healers, it helps us
understand what we should be
working toward. It helps us see
the life behind the disease.
A shaky hand can have a large
footprint.
[email protected]abdul-Kareem ahmed is a resident
in the department of neurosurgery
at the University of Maryland
Medical Center.Man found relief from his hand tremors with MRI-guided ultrasound surgery
“I’ve been playing
guitar, and I’m going to
start painting again.
Ninety to 95 percent of
my tremor is gone.”
73-year-old patient who underwent
the operationwomen who received placebos. It
took a randomized, controlled tri-
al — the gold standard in medi-
cine — to show that hormones
weren’t making women healthier
in old age. Instead, hormone-tak-
ers were healthier to begin with.
After those findings were re-
leased, the use of hormone thera-
py plummeted by as much as
80 percent.
Those 2002 findings weren’t
wrong, but they were reported in
a “very alarmist way,” s ays Stepha-
nie faubion, medical director of
the North American menopause
Society (NAmS) and author of
“mayo Clinic: The menopause So-
lution.” News headlines implied
that hormone therapy would give
women cancer or heart attacks,
but that was an oversimplifica-
tion, she says.
The study convincingly
showed that hormones shouldn’t
be taken long term for disease
prevention, but it did not directly
address their short-term use to
manage hot flashes and other
symptoms of menopause.
“A lot of nuance got lost along
the way,” says JoAnn manson,
chief of Preventive medicine at
Brigham and Women’s Hospital
and a lead investigator in the
WHI. The risk of breast cancer,
heart disease and other condi-
tions varied depending on how
old the woman was when she
started the therapy and whether
she took progesterone along with
the estrogen. (Women with an
intact uterus are advised to take
progesterone, too, to prevent the
endometrial lining from building
up and potentially developing
cancer.)Increased vs. lowered risks
The WHI has found that wom-
en in the study who took estrogen
and progesterone in combination
had an increased risk of coronary
heart disease, stroke, deep vein
thrombosis and breast cancer, but
women who took estrogen alone
actually had reduced risks of cor-
onary heart disease and breast
cancer. All of the women who took
hormones had reduced risk of
colorectal cancer, fractures, dia-
betes and all-cause mortality.
Those increases in heart dis-
ease and breast cancer risk sound
scary, but in absolute numbers,
the risks are pretty small, manson
says.
An analysis of the WHI data
manson and her colleagues pub-
lished in 2017 found that women
in the study who used hormone
therapy (whether estrogen alone
or with progesterone) for five to
seven years did not have an in-
creased risk of all-cause, cardio-
vascular or cancer mortality dur-
ing the 18-year follow-up. And for
women in their 50s, there was
actually a trend toward a reduced
risk of mortality, manson says.
But perhaps the most impor-
tant thing to understand, manson
says, is that the WHI was not
designed to look at hormones
used to address menopause
symptoms. Instead, it was exam-
ining whether they could reduce
chronic conditions such as stroke,
heart disease and cognitive de-
cline. It is like the difference be-
tween asking whether aspirin is
safe to take for a headache vs.
whether it is safe and effective to
take it on a daily basis in hopes of
preventing heart attacks.
The WHI results overturnedHormoNeS from e1 the idea that hormones should be
taken long term to stave off
chronic disease in postmeno-
pausal women, but it was not
specifically set up to assess the
safety of taking hormones short
term for relieving menopause
symptoms, manson says.
The average age at w hich wom-
en in the WHI started hormone
therapy was 63. That is 12 years
after the average age of meno-
pause, which means that using
the results of that study to predict
what will happen to women who
begin hormones when meno-
pause symptoms start and then
cease them when their symptoms
have ended is essentially compar-
ing apples and oranges.
There has never been much
doubt that hormones are a highly
effective way of treating symp-
toms such as hot flashes, night
sweats, mood swings and all the
problems like sleep disruption
that come with them.
“A s of 2020, hormone therapy
is still the best way to relieve
menopause symptoms,” says Na-
nette Santoro, chair of the depart-
ment of obstetrics and gynecolo-
gy at the University of Colorado
Anschutz medical Campus.
NAmS, the American Society
for reproductive medicine, and
the Endocrine Society all take the
position that hormone therapy is
appropriate for relief of hot flash-
es and vaginal dryness for most
healthy women who are recently
menopausal.
Hormones prescribed to meno-
pausal women are no longer
called “hormone replacement
therapy,” because the purpose is
not to replace what the ovary
previously made or to use them
indefinitely, but to manage meno-
pause symptoms, which can be
debilitating and disruptive, fau-
bion says.
“There’s plenty of data to show
that this presents a financial bur-
den to society in general and
women personally,” she says. “We
do women a disservice by patting
them on the head and saying
you’ll be all right, don’t worry
about it.”Not an elixir of youth
Hormone therapy is not a mag-
ic bullet or an elixir of youth, and
it shouldn’t be used willy-nilly,
manson says.
But women who are suffering
with menopause symptoms
should not be denied hormone
therapy, she says, unless they are
at increased risk of cardiovascu-
lar disease, breast cancer or other
estrogen-sensitive cancers.
(NAmS has a free app, menoPro,
that can help women determine
their risk profile.)
“The pendulum has swung
widely from the perception that
hormone therapy is good for all
women to the perception that it’s
all bad for all women, to now a
more appropriate place in be-
tween where hormone therapy is
perceived to be good for some but
not all women,” manson says.
“We’re recommending that hor-
mone therapy be used for the
duration that it’s needed to ad-
dress symptoms at the lowest ef-
fective dose and with ongoing
reassessment of the balance of
risks and benefits.”
The time to start therapy is as
soon as the symptoms start. “In-
tervening earlier, rather than lat-
er, actually seems to carry less
risk,” Santoro says.
once symptoms start, they areunlikely to get better soon. on
average, the menopause transi-
tion lasts about four years, San-
toro says. Some women have
symptoms that persist even lon-
ger, however. Although there are
exceptions, most women won’t g o
through menopause before 45,
Santoro says.
“If you’re 45 or older and start-
ing to have hot flashes, night
sweats or mood or sleep changes,
it could be your hormones and it
might be time to start some active
management,” she says.more choices now
To day, more options exist for
hormone treatments than when
the WHI study began. Women can
now choose pills, skin patches,
vaginal delivery products and
others. Vaginal estrogen is effec-
tive for treating vaginal dryness
that interferes with sex, Santoro
says, “and it’s a therapy that wom-
en can take long term with little
concern about any major side
effects as best we can tell.”
The optimal intervention de-
pends on the individual, but if a
woman needs birth control, a hor-
monal contraceptive can be a nice
way to “cruise through meno-
pause,” Santoro says. Dosing and
hormone type are important to
consider. Birth control pills typi-
cally have higher doses of hor-
mones than those given exclu-
sively to treat symptoms of meno-
pause, but other hormonal con-
traceptives may have less.
Some of Santoro’s p atients who
are taking birth control pills opt
to stay on them continuously,
without taking the week off each
month for a period. During peri-
menopause, that pill-free week
can make women miserable with
symptoms, so staying on the pill
continuously is one way to ease
the transition, Santoro says.
She works with patients to esti-
mate when they might be meno-
pausal based on their family his-
tory (your mother’s age at meno-
pause is a decent proxy for your
own) and their own menstrual
pattern.
“If you’re over 45 and have gone
60 days without a period and you
used to cycle normally, you’ve got
a 90 percent chance of being
menopausal within four years,”
Santoro says.
No test exists for menopause.
Levels of anti-müllerian hormone
can be predictive about the tim-
ing of menopause, but it’s not an
exact science, Santoro says. The
medical definition is that the
woman has gone one year with-
out a period, which means it can
be confirmed only in retrospect.
Such uncertainty can feel
daunting for someone going
through menopause, but infor-
mation can help.
“Women need to be empow-
ered to know what’s coming and
that they can do something about
it,” faubion says. It can be hard to
find a health-care provider who is
well-versed in menopause medi-
cine, but NAmS’s website, meno-
pause.org, can help women find
providers who have passed an
exam demonstrating their knowl-
edge about menopause.
There is a lot of negative mes-
saging about menopause, but
what is less often extolled are the
many upsides, Santoro says.
many women are happy to be
done with their periods and re-
lieved of having to deal with con-
traception.
[email protected]Advantages, risks of hormone therapy for women
Look for FDA-approved
‘bioidenticals’
the internet is awash with experts promoting
custom compounded “bioidentical” hormones.
the word “bioidentical” refers to hormones that
are similar to what the body naturally produces
vs. ones derived from animal urine or produced
synthetically. the expectation is that because
bioidenticals are more similar to what the body
naturally produces, they might have some
advantage, says Joann Manson, chief of
Preventive Medicine at Brigham and Women’s
hospital and a lead investigator in the Women’s
health initiative (Whi).
But “bioidentical” has become a marketing
term, and many of the products called
“bioidentical hormones” are compounded
drugs, which are neither approved nor subject
to oversight by the food and drug
administration, Manson says.
the “fda does not have evidence that
compounded ‘bioidentical hormones’ are safe
and effective, or safer or more effective than
fda-approved hormone therapy,” according to
an fda fact sheet. in 2008, the agency sent
warning letters to several compounding
pharmacies, calling them out for making
unsubstantiated claims about their “hormonal’
products.
Compounded bioidenticals also run the risk of
containing contaminants and impurities, and
they may provide inconsistent doses.
Unless someone has an allergy to an ingredient
in the product, experts say there is no good
reason to use a compounded bioidentical
product instead of one of the fda-approved
bioidenticals available at a regular pharmacy in
numerous forms — oral estradiol, transdermal
estradiol patches, gels, sprays, lotions,
estradiol vaginal creams, tablets, rings and
inserts, and micronized oral or vaginal
progesterone.
these products are produced with strict
manufacturing oversight, sold at regular
pharmacies and come with package inserts
that include a black box warning about
potential risks.
— Christie Aschwandenanna godeassi
for the Washington Post