Non-HRT Options for Menopausal Vasomotor Symptoms

Clonidine

Clonidine (Dixarit) is a centrally active alpha-2 adrenergic agonist and has been shown to reduce hot flushes in some, but not all trials. It is often used as first line treatment in a dose of 25mcg tablets, 2-3 twice daily.
Side effects include difficulty in sleeping, dry mouth, dizziness, constipation and sedation.
Interaction may occur with anti-hypertensives.

Selective Serotonin Reuptake Inhibitors

The belief that a variety of chemical reactions involving serotonin, noradrenalin and dopamine are instrumental in initiation of the flush, has led to trials of drugs that selectively inhibit the re-uptake of serotonin and noradrenalin.
Venlafaxine, a selective inhibitor of both serotonin and noradrenaline reuptake, in doses of 37.5mg, 75mg or 150mg daily, reduced flushes by 37, 61 and 61% compared to placebo reduction of 27% [Ref 11].
The usual starting dose is 37.5mg daily with gradual increase in dose to reduce risk of side effects, which include mouth dryness, dizziness, insomnia, agitation and confusion. In 2004 the CSM advised caution in the use of venlafaxine because of concerns about cardiotoxicity and toxicity in overdose. It recommended that treatment with venlafaxine should only be initiated by specialist mental health practitioners. It should not be used in patients with heart disease, electrolyte imbalance or in patients who are hypertensive.
Paroxitene, 12.5-25mg daily, has been shown to produce a 50% reduction in flushes, and Fluoxitene, 20mg daily has also been reported as producing 60% reduction.
Interactions common to these SSRIs may occur with MAOIs, CNS active drugs and warfarin.

Progestogens

Megestrol acetate (Megace), a synthetic progestogen, has been shown to reduce hot flushes by 85% compared to a placebo effect of 21% when given in a dose of 20 to 80mg daily [Ref 18]. A transient increase in hot flushes has been noted in the first two weeks of therapy. There is a theoretical possibility of adrenal suppression since megestrol acetate has glucocorticoid activity, leading to adrenal insufficiency after discontinuation.
Other progestogens shown to be effective include Medroxyprogesterone acetate (Provera), 20-100mg daily, and Norethisterone (Primolut), 5-10mg daily.
Progestogens used in fairly high dose may confer an increased risk of venous thromboembolism and weight gain is a common progestogenic side effect.

Gabapentin

Gabapentin, a GABA analogue, used in doses of 300-1600mg daily, has been shown in a randomized, placebo controlled study to reduce flushes by 45% [Ref 12]. Gabapentin may be beneficial for the symptoms of aches, pains and paraesthesia which many menopausal women experience.
Interaction may occur with antacids and side effects include dizziness, fatigue, tremor, ataxia, arthralgia and weight increase. Side effects can be reduced by gradually increasing the dose.

Progesterone cream

Natural progesterone cream is only available on a private prescription. Two recent studies produced conflicting results on effect on vasomotor symptoms; one showing a small reduction and the other showing no change [Refs 19 and 20]. Progesterone cream should not be used for endometrial protection in women taking systemic estrogen due to lack of effect. It should be noted that HRT and Clonidine are the only prescribed therapies that are currently licensed for treatment of menopausal vasomotor symptoms.