Oestrogen and raloxifene

What they are

Oestrogens influence dopamine activity, the energy supply of nerve cells and the body’s stress system. Low oestrogen levels are linked to more severe psychosis, and antipsychotics that raise the hormone prolactin can lower oestrogen.¹ Estradiol is the body’s main oestrogen; raloxifene acts like oestrogen in some tissues and blocks it in others.¹

How well they work

In a trial, 183 women with treatment-resistant schizophrenia wore an estradiol patch at one of two doses, or a placebo, for eight weeks; symptoms improved more on both doses.² In a trial of 200 women of childbearing age, hallucinations and delusions eased slightly, and only in women older than 38.³

Raloxifene improved symptoms in 56 women with treatment-resistant illness,⁴ but in 200 severely ill women after the menopause, placebo did better.⁵ A Dutch–Belgian trial included 102 people, about a quarter of them women. Overall, raloxifene did not help; women had fewer negative symptoms after 6 and 12 weeks, while men’s working memory was worse at 38 weeks.⁶ Pooled across 10 studies, raloxifene improved symptoms by about 7 points.⁷

In Finnish health records, women with schizophrenia who used menopausal hormone therapy relapsed less often, by about a sixth. This was an observational study.⁸

Side effects

In the estradiol trial among women of childbearing age, breast tenderness affected 15 women on estradiol and 1 on placebo, and weight gain 14 and 1.³ In the raloxifene trials, side effects were about as common as on placebo.^4,6

What we don’t know yet

• Which women benefit, by age and stage of life.
• Whether these treatments help men.