This document discusses the treatment of hot flashes. It begins by describing the clinical manifestations, pathophysiology, prevalence, and risk factors of hot flashes. It then discusses methods of assessing hot flash severity, including hot flash scores, the Greene Climacteric Score, and the Modified Kupperman Index. The main treatment approaches covered are hormonal therapies like estrogen, progestin, and tibolone, and non-hormonal options such as SSRIs, SNRIs, and complementary therapies. Hormonal therapies are generally the most effective treatment but have risks, so non-hormonal alternatives are considered when hormones are not appropriate.

1. Treatment of hot flashes
Aboubakr Elnashar
Banha university Hospital, Egypt
AboubakrElnashar

2. CONTENTS
1. INTRODUCTION
Clinical manifestations
Pathophysiology
Rate
Prevalence
Risk factors
2. ASSESSMENT
3. TREATMENT
4. TREATMENT OF INTRACTABLE HOT
FLUSHES
 CONCLUSION
4
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3. Score Calculation Interpretation
Severity score = (number of
mild hot flashes/day × 1) +
(number of moderate hot
flashes/day × 2) + (number of
severe hot flashes/day × 3) +
(number of very severe hot
flashes/day × 4)/total number
of hot flashes/day
Some trial methodologies deviate from this formula
slightly, excluding hot flashes in the very severe
category and including them in the severe category
Higher scores indicate
worse symptoms
There is no maximum
score since the score is
patient dependent for both
number and severity
2. ASSESSMENT
Hot Flash Score
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4. Score Calculation Interpretation
Assesses four subcomponents
of both symptoms and quality
of life: psychological (possible
score 0-33), somatic (0-21),
vasomotor symptoms (0-6),
and sexual (0-3)
Total score can range
from 0-63
Higher scores indicate
worse symptoms
For the vasomotor
subscore, a score of 0-2
indicates no or mild hot
flashes and 3-6 indicates
moderate-to-severe hot
flashes
Greene Climacteric Score
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5. Score Calculation Interpretation
Assesses 11 subcomponents: hot flashes,
sweating, insomnia, nervousness,
depression, vertigo, tiredness, joint ache,
headache, palpitations, and vaginal
dryness
All are scored from 0-3 based on
symptoms: 0 = none, 1 = weak, 2 =
moderate, 3 = strong
Hot flash score is multiplied by 4; sweating,
insomnia, and nervousness scores are multiplied
by 2; then all subcomponents are added together
for the total score
Total score
can range
from 0-51
Higher scores
indicate
worse
symptoms
Modified Kupperman Index
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6. A. Hormonal
1. Estrogen
2. Progestin
3. Tibolone
4. Bioidentical hormones
B. Non-hormonal
I. CNS agents
1. SSRI, SNRI
2. Gabapentin
II. Complementary and
Alternative Medicine
1. Acupuncture
2. Phytoestrogen
3. Phytoprogestin
4. Lifestyle Changes
4. TREATMENT
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7. A. Hormonal
1. ESTROGEN
Indication
 Moderate-to-severe hot flashes: Short-term (2-3y,
not ≥5y)
[NAMS, 2010].
Long-term use is no longer recommended.
Mild hot flashes: do not usually require any
pharmacologic intervention.
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8. Effectiveness.
Systemic ET
Most effective tt for VMS
•stop hot flashes completely in 80%
•reduce frequency and severity in the remainder
[Maclennan et al Cochrane Database Syst Rev 2004].
Only therapy currently approved by the FDA
(Shifren, 2010).
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9. Route.
Oral, parenteral, topical, vaginal, or transdermal:
similar effects.
Oral:
Most popular, although
Transdermal
±safer {avoid liver’s1st pass effect}
≥convenience {less frequent administration
(once or twice weekly)}.
similar efficacy {all absorbed from GIT primarily as estrone
sulfate, which is continuously desulfated and converted to E2}: even
though oral estrogen is administered in a single daily dose, the resulting
serum E2 vary little between doses.
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10. Uterus
Sequential therapy without tablet break
Regular bleeding at end of cycle
How is HRT Given?
Continuous Sequential HRT
Estrogen
Progestogen
Day 14
De Villiers TJ et al. 2013.
.
Continuous Estrogen
Estrogen
No tablet break
No bleeding as no uterus
Uterus
Continuous Combined HRT
Estrogen
Progestogen
Day 14 Combined therapy without tablet break
No bleeding at end of cycle
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11. Estrogen contraindications:
Undiagnosed abnormal genital bleeding
Known, suspected, or history of breast cancer
Known or suspected E-dependent neoplasia
Active DVT, pulmonary embolism, or history of
these conditions
Active or recent (within the past year) arterial
thromboembolic disease (stroke or MI)
Liver dysfunction or disease
Known hypersensitivity to the ingredients of E
preparation
Known or suspected pregnancy.
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12. When prescribing of HRT:
 Timing:
 Sooner is better
 : Maintain the beneficial action of E
 Personalization:
 Tailor the type, dose, and route.
 No one preparation that suits all women.
 Select the right dose for the right woman.
 Balance the benefits vs. the risks
At both the initiation of therapy and over time.
 With age:
Continuation and tapering the dose {Hot flashes gradually subside
without therapy in most postmenopausal women}

13. 2. Progestin
Progestin alone
Somewhat effective for tt of hot flashes {inhibit GnT
secretion and increase endogenous hypothalamic
opioid peptide activity}.
Combined with E:
Protect against E-induced endometrial hyperplasia.
Slightly more effective than E alone in ameliorating
hot flashes.
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14. Role of Progestogens in HRT
Writing Group for the PEPI Trial. JAMA 1996;275:370–5.
PEPI Trial: multicenter RCT : Results of Endometrial Biopsy
Adding a progestogen is needed to safeguard the
endometrium
Placebo CEE
alone
CEE+MPA
sequential
CEE+MPA
continuous
119 119 118 120
Normal 98% 38% 95% 99%
Simple
hyperplasia
1% 28% 3% 1%
Complex
hyperplasia
1% 23% 2% 0%
Atypia 0% 12% 0% 0%
Adenocarcinoma 1% 0% 0% 0%
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15. 3. Tibolone
Synthetic steroid: 17 OH -7 methyl norpregn
Action
3 metabolites, each with different binding affinity to
the E, P & A receptors.
Weak estrogenic, progestagenic & androgenic
(Gonadomimetic)
It is anti E on the endometrium & E on the vagina
2.5 mg/d
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16. Widely used in Europe and other countries for
nearly 20 years
Reduces VMS when compared to placebo
[NAMS, 2004]
 Beneficial effect on BMD.
Modest effect on symptoms of sexual dysfunction.
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17. Compared to placebo:
Tibolone:
More effective in relieving the frequency of VMS
Increased vaginal bleeding
Compared to equipotent doses of combined HT:
Tibolone
Reduced vaginal bleeding
Less effective in relieving the frequency of VMS
(Formoso et al, 2012: Cochrane Database Syst Rev)
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18. Long term safety:
•RCT of 3098 women with breast cancer and
menopausal symptoms was halted after 3.1 y
{increased tumour recurrence} .
•RCT of 4506 of osteoporotic women with negative
mammograms
Reduction in breast cancer compared to placebo
after 2.8 y
An excess risk of stroke in women whose mean
age was over 60 y.
(Formoso et al, 2012: Cochrane Database Syst Rev)AboubakrElnashar

19. No clear evidence of tibolone effect on endometrial
cancer compared with placebo.
No evidence of a difference in long term safety
between tibolone and combined HT.
Similar concerns may exist for EP therapy but
overall benefit-risk profile
better known
more directly related to women with menopausal
symptoms.
(Formoso et al, 2012: Cochrane Database Syst Rev)
AboubakrElnashar

20. B. Non hormonal
I. CNS agents
1. SSRI, SNRI
2. Gabapentin
II. Complementary and Alternative Medicine
(CAM)
1. Acupuncture
2. Phytoestrogen
3. Phytoprogestin
4. Lifestyle Changes
AboubakrElnashar

21. B. Non hormonal
 Mild hot flashes: usually do not seek or require
pharmacologic intervention.
 However, women often try
{NAMS; 2004]
1. Lifestyle changes
(keeping the core body temp cool and regular exercise),
either alone or combined with
2. Nonprescription therapies
(soy foods, isoflavone supplements (from either soy or red
clover, black cohosh, or vitamin E).
 Neither exercise nor nonprescription therapies
have proven benefit.
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22. Non hormonal tts:
No FDA-approval for tt of hot flashes
Long-term studies: not available.
Short-term trials: available
Indication:
1. Women decline HT
2. E is contraindicated.
{many side effects or ineffectiveness compared with
HT: limits their routine use
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23. I. Central Nervous System Agents
1. Selective Serotonin-Reuptake Inhibitors(SSRI).
selective serotonin norepinephrine reuptake
inhibitors (SNRIs)
RCT:
SSRI: Venlafaxine (Effexor)
Fluoxetine (Prozac, Sarafem)
Paroxetine (Paxil)
SNRI: Desvenlafaxine (Pristiq)
: modest improvement in hot flashes compared with
placebo.
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24. AboubakrElnashar

25. Benefits should be balanced against side effects:
nausea, diarrhea, headache, insomnia, fatigue, and
sexual dysfunction.
Caution in breast cancer receiving tamoxifen
{reduce the metabolism of tamoxifen to its most
active metabolite, endoxifen},
Reserve SSRI tt of hot flushes for women with
breast cancer receiving aromatase inhibitors or no
adjuvant tt.
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26. Pooled analyses (Lobrinzi et al, 2009)
of 7 trials of antidepressants and 3 trials of
Gabapentin
[Pandya et al, 2005 ].
The mean reduction in hot flash score with
placebo: 24%.
The additional hot flash score reductions Vs
placebo for
Paroxetine: 41%
Gabapentin: 36%
Venlafaxine: 33%
Fluoxetine: 13%
Although these agents do not appear to be as
effective as E for hot flashes, they are significantly
better than placebo.
AboubakrElnashar

27. II. Complementary and Alternative Medicine
(CAM)
Prevalence of use in postmenopausal women
Increasing (Newton, 2002).
50 to 75% [Keenan et al, 2003]
Higher in breast cancer patients.
Safety and efficacy
Not well established.
Soy and black cohosh: no more effective than
placebo
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28. 4. TREATMENT OF INTRACTABLE HOT FLASHES
Define
continuing occurrence of hot flashes despite the
administration of what should be an effective dose of
E.
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29. 1. Exclude other
potential causes
of flushes
hyperthyroidism,
malignancy
infection

30. 2. Exclude drugs that
 Decrease the absorption of E
 broad-spectrum antibiotics
 Increase the metabolism of E
{increase hepatic enzyme activity}:
 Barbiturates
 Anticonvulsants
 Tranquilizers
Stop or replace these drugs
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31. 3. Changing the route of E administration from oral
to transdermal: ± control of hot flashes by
bypassing the liver.
Titration of patch size until plasma E2 levels reach
120 pg/mL
No clinical trial data to support this approach.
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32. 4. Finally, for women who are receiving very high
doses of E:
Stop E for 1-2 w and then Restart at the usual dose
:give the woman a chance to compare the severity
of hot flashes on and off E.
±decide that, although the flashes have not
completely disappeared, E is beneficial
± tolerate the residual flashes better.
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33. CONCLUSION
HRT remains the most effective therapy for VMS
For moderate-to-severe VMS (and no history of
breast cancer or CVD): short-term E therapy is the
tt of choice (Grade 2B). 2-3 y and not ≥5 y.
Gradually taper after 1-2 y
Use lowest effective dose
Start earlier in menopause
.
.

34. If E is contraindicated or not well tolerated, or for
women who have stopped E and are experiencing recurrent symptoms but wish to
avoid resuming E: Gabapentin, SNRI, or SSRI (Grade 2B).
For women with breast cancer and hot flashes: no
phytoestrogens or black cohosh (Grade 2C).
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35. Invitation

36. Aboubakr Elnashar Lectures
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