Hot flashes; Any non-hormonal help ?

1. Hot flashes; Any non-
hormonal help ?
AHMED MOUSTAFA AL-AMELY

2. Symptoms
• Hot flashes can occur day or night; when they
occur at night, they are called night sweats.
• Each episode lasts 3–10 minutes and can recur
with varying frequency .
• Some women experience hot flashes hourly or
daily, whereas for others they may occur
occasionally.
• Furthermore, the majority of women have hot
flashes for 1–2 years, but ∼15% may have
persistent hot flashes for up to 30 years.

3. The Japanese experience (hotto furasshu)
• They asked the Japanese women (and their physicians) how they would describe this time of life
and the symptoms they experienced.
• The respondents used a combination of 3 terms :
 Sudden feeling of heat
 Feeling hot or flushed
 Rush of blood to the head

4. PATHOPHYSIOLOGY
• Hot flashes (HFs) are characterized by excessive vasodilatation of peripheral vasculature to lose heat in
setting of abnormal hypothalamic thermoneutral zone.
• While normal women initiate mechanisms of heat loss, once core body temperature increases by 0.4°C,
women with HFs initiate vasodilatory response with a much smaller increase in core body temperature. It
is peripheral vasodilatory response that results in profuse sweating and sensation of intense heat.
• During HFs, the peripheral vasodilation results in loss of heat with lowering of core body temperature
and abolition of flush. The chills which accompany HFs are a compensatory response to bring lowered
core body temperature to normal.

5. Management (Non-hormonal)
• The management of HFs is guided by their frequency and severity.
• The severity of HFs can be graded as:
 (a) mild (no interference with usual daily activities)
 (b) moderate (interfere with usual daily activities to some extent)
 (c) severe (when usual daily activities cannot be performed)
• In mild cases: Just avoid the triggers, diet modification and lifestyle changes.
• In moderate to severe cases: Start herbal medications  If inadequate response  Start SSRIs/SNRIs ( Be
familiar with one drug and always use it)  If inadequate response  Try another SSRIs/SNRIs  If inadequate
response  Try gabapentin alone or in combination with SSRIs  If inadequate response  Give a trial of
clonidine

6. Knowing the triggers of hot flashes
• Identify your own hot flashes triggers and avoid them. ( e.g. Some women notice hot flashes when
they eat a lot of sugar)

7. Diet Modification
• Avoid caffeine, spicy food, hot drinks and alcohol.
• Try to incorporate more plant estrogens into your diet.
• Plant estrogens, such as isoflavones, are thought to have weak estrogen-like effects that may reduce hot flashes.
• Examples of plant estrogens include:
 Soybeans ‫الصويا‬ ‫فول‬
 Chickpeas ‫الحمص‬
 Lentils ‫العدس‬
 Flaxseed ‫الكتان‬ ‫بذور‬
 Grains, beans, fruits, red clover and vegetables.

8. Lifestyle changes (Behavioral modifications)
• Patients should maintain a low core body temperature through:
 Reducing the temperature in your bedroom.
 Dressing loose-fitting and light clothes.
 Using a fan as needed.
 Take a warm bath or shower at bedtime.
 Consuming cool or cold food or drinks. (drinking small amounts of cold water or milk products before bed)
• Weight loss
• Relaxation techniques
 Try deep, slow abdominal breathing (6 to 8 breaths per minute). Practice deep breathing for 15 minutes in the morning, 15 minutes
in the evening and at the onset of hot flashes.
 These techniques may reduce overall sympathetic tone, thus reducing the frequency of hot flashes.

9. Medications
• Herbal (Over-the-counter) Medications
 Black cohosh
 Evening primrose oil
 Soy (Phytoestrogens)
 Vitamin E
• Neuroactive agents
SSRIs and SNRIs
Gabapentin and pregabalin
 Clonidine

10. Black cohosh
• Native American women have used the extract of black cohosh (Actae racemosa or Cimicifugae racemosae) for
centuries as a phytotherapic cure for many different conditions. Nowadays, is used only for climacteric symptoms.
• The mechanism underlying the bioactivity of black cohosh is still unclear. Selective modulation of oestrogen
receptors (SERM), serotonin partial agonist mechanism, antioxidant and anti-inflammatory effects have been
suggested.
• Dose : 20-80 mg / day
• Side effects:
Mild stomach upset.
 Safe up to 6 months only due to possible estrogen-like effects. ( Not recommended in women with breast cancer)
 Liver toxicity has been reported.

11. Evening primrose oil
• Side effects:
 Nausea
 Diarrhea
 Headache.

12. Soy (Plant estrogen) (Phytoestrogens)
• Side effects:
 Appears safe if consumed in foods. In supplement form, consistency of dose and quality can be a
concern.
Supplements are not recommended for breast cancer survivors.

13. Vitamin E
• Side effects:
 13% increase risk of heart failure. Might increase death rate in those who use high doses for a
long time.
 Excessive vitamin E intake can interfere with blood clotting and lead to fatal bleeding.

14. Selective serotonin reuptake inhibitors
(SSRIs) ( Anti-depressants)
• Paroxetine ( 10-20 mg daily ) (Tradename: paroxetine)
• Citalopram ( 10-20 mg daily ) (Tradename: Cipram)
• Escitalopram ( 10-20 mg daily ) (Tradename: Cipralex)

15. Selective serotonin-norepinephrine
reuptake inhibitors (SNRIs)
• Duloxetine 30-120 mg/ day (Tradename: Duloxeprin)
• Venlafaxine 37.5- 150 mg/ day (Tradename: Efexor)
• Desvenlafaxine 100-150 mg/ day (Tradename: Pristiq)

16. SSRIs dosing
• Start with a low dose, increasing gradually over 2-4 weeks as tolerated.
• Most SSRIs are taken in the morning to minimize insomnia, but if it makes the patient sleepy, it can be taken at
night.
• When SSRIs are to be discontinued, gradually reduce the dose over 2 weeks to minimize symptoms that con occur
from withdrawing.
• Start with dose 10 mg (a half of a tablet) daily for one week, and then increase to 20 mg daily.
• Take tablets with or without food, once a day and at the same time each day.
• If after 4-6 weeks there is no benefit or significant side effects, treatment should be stopped.
• When changing from one SSRI to another SSRI or SNRI, wait for SSRI free period to prevent side effects due to
drug interactions.

17. SNRIs dosing
• Venlafaxine (Efexor)
 Available in 37.5,75,and 150mg capsules,
 Start the dose at 37.5mg daily.
 The dose can be increased every week until the recommended dose is reached, which is 75mg
daily.
 Take with food to decrease any nausea feeling, at the same time everyday.
 Gradually withdraw over 2 weeks to avoid withdrawal symptoms.

18. SSRIs and SNRIs
• SSRIs and SNRIs act rapidly, with a decrease in vasomotor symptoms as early as after 2 weeks of treatment.
• Among SSRIs and SNRIs: paroxetine, citalopram and escitalopram carry the best safety profiles.
• Escitalopram (Cipralex) is one of the first line options for hot flashes due to its favorable tolerability profile,
it is considered the antidepressant with the highest number of days of uninterrupted treatment, the best
adherence to treatment and the lowest proportion of switching to other drugs.
• Side effects:
 Nausea, asthenia, dizziness, sleep disturbances, dry mouth, constipation and sexual dysfunction.
 SNRIs can increase blood pressure; therefore, this variable should be monitored in all patients
• For women, who do not respond to one SSRI/SNRI, use another SSRI/SNRI before switching to another class
of drugs. In case, these are ineffective or not tolerated, consider administration of gabapentin

19. SSRIs and SNRIs in breast cancer patients
• For women with breast cancer, potential interference of antidepressants with tamoxifen since some
SSRIs and SNRIs can inhibit CYP2D6 enzyme with a consequent decrease in the formation of the active
metabolite from inactive tamoxifen.
• Among SSRIs, paroxetine and fluoxetine are the most potent inhibitors and they should be avoided
during tamoxifen use; on the contrary, citalopram and escitalopram only have a limited inhibitory effect
and can be used in tamoxifen users.
• Among SNRIs, venlafaxine and desvenlafaxine are the safest choices while using tamoxifen
• Contraindications to SSRIs and SNRIs use include: previous neuroleptic and serotonin syndrome, the
current use of monoamine oxidase inhibitors, bipolar disease, uncontrolled seizures, liver or kidney
insufficiency, and hypertension for SNRIs users.

20. Gabapentin and pregabalin
• Gabapentin: (Neurontin , available as 100mg, 300mg and 400mg capsules)
 Dose (300-900 mg/day)
 Compared to SSRIs/SNRIs, gabapentin is as effective but has more side effects
• Pregabalin: (Lyrica)
Dose ( 150-300 mg/day)
Pregabalin is effective in HFs relief but it is less studied than gabapentin
• Side effects:
drowsiness, unsteadiness and dizziness in up to 50% in postmenopausal healthy women
possible suicidal thoughts and behaviors with gabapentin and pregabalin

21. Gabapentin and pregabalin
• Gabapentin and pregabalin are anticonvulsant drugs able to decrease the frequency of HFs by binding to calcium
channels located in the hypothalamus and, consequently, better modulating thermoregulatory activity.
• Gabapentin may be a better choice for women with predominant nocturnal HFs for its added benefit on the
maintenance of sleep cycle. It is as effective as venlafaxine, but patients often prefer venlafaxine due to better
tolerance profile of later.
• The dosage of gabapentin needs to be individualized. Generally, start with 300mg daily as single dose at night
time because it can make the patient little dizzy and sleepy. The dose can be increased by 300mg every 2-3 days
until the recommended dose is reached, which is 300mg three times daily (900mg).
•While switching therapy from SSRI/SNRI to gabapentin, it is preferable to continue SSRI/SNRI for 1st 2 weeks while
gabapentin is being introduced and taking its full effect.
• The other drugs (clonidine and pregabalin) are used only infrequently for the management of HFs.

22. Clonidine
• Clonidine is an anti-hypertensive alpha-adrenergic agonist, which may inhibit flushing by
reducing peripheral vascular reactivity. However, the exact mechanism of action is still
unclear.
• Tradename : Catapres, available as 100 and 150 micrograms (mcg) tablets.
• Start the dose at 25 mcg ( a quarter of a tablet) twice daily. The dose can be increased as
tolerated to 50-75 mcg twice daily over two weeks if necessary.
• If after 2-4 weeks there is no noticeable benefit or significant side effects, treatment
should be stopped.
• However, significant side effects (dry moouth, dizziness, constipation, hypotension and
potential hypertension, if suddenly interrupted) have been often reported with clonidine
and, due to safety problems, its clinical use is poor.

23. Thank you
.