HRT in Premature ovarian failure

• Hormone therapy (HT) ***mainstay of treatment

• until the average age of the natural menopause.
• Combination HT + estrogen/progestogen contraceptive pill.
• HRT may need a higher dose of estrogen (compare)
• estrogen replacement -- increases the risk of breast cancer.
• despite adequate doses of estrogen replacement – reduced libido
Managing premature ovarian insufficiency
(NICE Guideline)
1) Sex steroid replacement + HRT / combined hormonal contraceptive
2) Education :
• Importance of start hormonal tx + HRT / combined hormonal contraceptive
• Continue treatment till age natural menopause (unlesss contraindicated)
• Risk breast cancer & CVS dss ↑ with age
• HRT (+) BP
• HRT & combined oral contraceptive (+) Bone protection
• HRT – not contraceptive
3) Contraindicated for hormone tx:
• Advice – Bone and CVS health
• Symptom management
4) Refer for psychosocial health related to their condition
ALTERNATIVE AND
COMPLEMENTARY
THERAPIES
 Alternatives to HRT
• Why would I choose an alternative to HRT?
• Contraindicated due to personal or family’s history, e.g. breast cancer or deep
vein thrombosis (DVT - a blood clot in a deep vein)
• Patient want an alternative treatment that works especially well for one
particular symptom
• Pateint concerns about the safety and side effects of HRT
 What are the alternatives to HRT?
The alternatives to HRT can be broadly classified as:
• Herbal medicine - a practice based on the use of plants or plant extracts to
relieve symptoms, e.g. evening primrose oil or St John’s Wort
• Alternative medicine - a range of therapies used instead of conventional
medicine, such as acupressure, acupuncture and homeopathy
• Complementary therapy - interventions that tend to be used alongside
conventional medicine, e.g. aromatherapy with HRT
• Non-hormonal medical treatments - treatments prescribed by doctor –
SSRI/SNRI, gabapentin, etc.
List of non-prescription therapies commonly used in the treatment of
menopausal symptoms
RCOG (patient leaflet)
• little evidence for the efficacy and safety of most of them.
• These products are currently unregulated in the UK
• majority are likely to be harmless
• Number of serious & fatal interactions

Complementary therapies and unregulated

preparations (NICE guideline)
• Explain to women that the efficacy and safety of
unregulated compounded bioidentical hormones
are unknown.
• Explain to women who wish to try complementary
therapies that the quality, purity and constituents
of products may be unknown.
• St John's wort may be of benefit in the relief of
vasomotor symptoms, there is uncertainty about:
• appropriate doses
persistence of effect
variation in the nature and potency of preparations
Lifestyle
• changes in diet
• RCOG – low caffeine and alcohol
reduce hot flushes and night
sweats.
• Supplement : Vit E
• Exercise & regular physical
activity – aerobic, yoga
• Smoking cessation
• avoid excessive weight gain.
Phytoestrogens: soy and red clover
• Use: for reducing hot flushes and night sweats in peri-
or postmenopausal
• Trials red clover vs placebo
• Trials soy vs placebo
• Review:
• no evidence that phytoestrogen treatments helped to relieve
menopausal symptoms.
• produce a slight to modest reduction in the number of daily
flushes in menopausal women
• A soy-derived preparation, DT56a (+)ve - hot flush reduction
• Estrogenic actions -- interactions with tamoxifen.
 Black cohosh
• RCOG –
• Use: Alleviate menopausal symptoms
• There is no consensus as to the mechanism by which it
relieves hot flushes. (RCOG)
• BMS
• Use: help in hot flushes
• Black cohosh does not help with anxiety or low mood
• Cons:
• estrogenic actions **debated -- use in women with
hormone-sensitive conditions.
• Little is known about safety.
• interact with other medicines and there are unknown risks
regarding safety

• Liver toxicity has been reported (caution label)

 St John’s wort
• Use:
• RCOG
• efficacious in mild to moderate depression in both peri- and
premenopausal women because of its SSRI-type effect
• efficacy for vasomotor symptoms remains to be proved.
• improved menopause-specific quality of life and a nonsignificant
improvement in hot flushes
• BMS- relieving vasomotor symptoms
• Cons:
• It interacts with many medication
• It may cause breakthrough bleeding and contraceptive failure
• BMS- not with Tamoxifen
Dong Quai
• RCOG
• Use: Vasomotor symptoms
• Benefit over placebo was found only for mild hot flushes.
• BMS - not shown to improve hot flushes, anxiety or low mood

• Cons:
• Interactions with warfarin, increasing the risk of bleeding and
photosensitisation

Ginseng
• RCOG- Not better than placebo for vasomotor
symptoms.
• BMS- not shown to improve hot flushes, anxiety or low
mood
• Cons:
• interactions have been observed with warfarin, phenelzine
and alcohol.
Evening Primrose oil
RCOG
• no evidence for its efficacy in the menopause.
• ineffective for treating hot flushes.

Agnus Castus (chasteberry)

• Combination-reduced vasomotor symptoms (RCT)

• Ginkgo biloba, hops, sage leaf, liquorice and valerian root

(Popular) - no evidence on menopausal symptoms.

• Kava kava (Piper methysticum), - for anxiety, including that

associated with the menopause****
• banned in the UK because of reports of liver damage with the herb.
Acupuncture- Evidence helps menopausal symptoms is
conflicting.

Reflexology - reduction in symptoms in both groups

Magnetism - no evidence of benefit at present

Homeopathy - Limitation small RCT

Stellate ganglion blockade

• for hot flushes and sweating
• refractory to other treatments
or where HRT is contraindicated
Dehydroepiandrosterone (DHEA)
• Use
• antiageing effects in postmenopausal women
• benefits on the skeleton, cognition, wellbeing, libido and the vagina.
• improving fertility outcomes.
• modest reduction in hot flushes
List of
prescription
therapies
commonly
used in the
treatment of
menopausal
symptoms
 Non-hormonal treatment
• SSRI and SNRIs ***most commonly used in clinical practice for the
alleviation of menopause symptoms as an alternative to HRT.
• Use:
• Depression
• Anxiety
• improve hot flushes in some women.
• Paroxetine ***Menopausal hotflush
• Other SSRIs - citalopram and fluoxetine.
• Breast cancer survivor - Venlafaxine. (*** Should not take fluoxetine / paroxetine)
• Side effect:
• dry mouth
• Nausea***
• Constipation
• appetite problems
• reduction in libido
• very unwanted extra effect for menopausal women.
Gamma aminobutyric acid (gabapentin):
• Use: improve flushes and sweats.
• Side effects :
• sleepiness
• dizziness
• weight gain
• dry mouth
Alpha-2-agonist: Clonidine – the only non-hormonal drug licenced for hot
flushes in the UK
• Side effect:
• sleep disturbance
• Rebound high blood
Biphosphonates (Alternative: SERM- Strontium & Raloxifene)
• Use: For osteoporosis prevention
• significant side effects only women over 60 who are at high risk of osteoporosis.
Beta-blockers
• treating vasomotor symptoms (small trials)

Progestogens
• Use
• Popular alternative to combined HRT in women with intractable vasomotor symptoms and
contraindications to estrogen, such as breast and uterine cancer or venous thromboembolism***.
• Cons – Increase risk breast cancer.
Psychological treatments (RCOG) & BMS
- CBT (COGNITIVE BEHAVIOURAL THERAPY
• for low mood or anxiety related to menopause.
• also improve hot flushes and sweats.

• The North American Menopause Society (NAMS) recommends a CBT

approach that combines:
• relaxation techniques
• sleep hygiene
• learning to take positive healthy attitude to a menopause challenge.
Treatments for breast cancer survivors
• *** safety of possibly using estrogen-based therapies for some
of these women, particularly in receptor negative patients,
• ***most clinical guidelines will not recommend estrogen based
treatments.
• The North American Menopause Society (NAMS) recommends
- SSRIs, SNRIs, Gabapentin, Pregablin, Clonidine, CBT
• The UK NICE guidelines (November 2015)indicate that
• SSRIs,SNRIs and Gabapentin are no better than placebo
• Paroxetine and Fluoxetine may reduce the efficacy of Tamoxifen.
• St John’s Wort not recommended because of serious drug interactions.
 Final say on alternative tx:
Prescribing alternative mainly by:
1) Patient preference
2) contraindications to traditional HRT.
3) advantages and disadvantages in a balanced evidence-based manner.
4) Risk factor
1) advantages and disadvantages of using HRT and the alternatives based on symptom
severity
2) quality of life

• Efficacy alternative (50-60%) < traditional HRT (80-90%)

• The trials small and of short duration  limited value in determining efficacy
and safety.
• Alternatives are with their own adverse effects and risks, which have
necessitated warnings being issued by regulatory bodies for some products.