How can amenorrhea due to antipsychotics be treated?

Doctor's Answers (2)

Dr Beng Yeong Ng

"Psychiatrist with over 20 years of experience"

Thank you for highlighting such a predicament – amenorrhoea and psychiatric condition. Amenorrhea (uh-men-o-REE-uh) refers to the absence of menstruation — one or more missed menstrual periods. Women who have missed at least three menstrual periods in a row have amenorrhea.

Patients with high emotional stress may have amenorrhea or menstrual irregularities related to abnormal hypothalamic functions. Anorexia nervosa has been shown to cause hypothalamic dysfunction, leading to amenorrhea. In depressed women, estradiol (female hormone) levels are lower than in euthymic women, probably because of altered hypothalamic-pituitary axis (HPA) function. Also, physical distress is correlated with menses disruption.

Medications can cause amenorrhea, primarily through hyperprolactinemia—although other mechanisms may be involved. Prolactin suppresses hypothalamic luteinizing hormone-releasing hormone (LHRH) production, leading to decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH), thus reducing circulating estrogen (female hormone). Prolactin-secreting pituitary tumours and drug side effects most commonly cause hyperprolactinemia.

The degree of rise in prolactin level is helpful in determining whether the elevation can best be attributed to use of antipsychotic drugs or another cause. If the prolactin level is less than 2,000 mIU/L (∼95 ng/mL), elevated numbers are more likely due to the use of antipsychotic medication. If the level is greater than 2,500 mIU/L (∼118 mg/mL), in the absence of breast-feeding or pregnancy, a pituitary tumor may be suspected.

The primary symptom of secondary amenorrhea is missing several menstrual periods in a row. Women may also experience:

• acne

• vaginal dryness

• deepening of the voice

• excessive or unwanted hair growth on the body

• headaches

• changes in vision

• nipple discharge

Phenothiazines such as chlorpromazine, butyrophenones such as haloperidol, and the atypical antipsychotic risperidone raise prolactin levels via dopamine-receptor antagonism. Other atypical antipsychotics—including aripiprazole, clozapine, olanzapine and quetiapine —are associated with lower serum prolactin levels than risperidone. Preliminary studies suggest, for example, that switching patients from risperidone to quetiapine may help resume menstruation without worsening psychotic symptoms, and that amenorrhea often resolves after the patient is switched to another atypical antipsychotic.

Some studies have suggested treatment strategies using aripiprazole as an adjunct to reduce the prolactin level in patients treated with antipsychotics. Particularly in patients who are clinically stable on antipsychotic treatment, discontinuing current medication and switching to an atypical antipsychotic may be inappropriate, so adjunctive therapy may be a better strategy. The rationale of aripiprazole’s use as an adjunct may be attributed to its dual agonism/antagonism at the dopamine D2 receptor, which may mitigate the effects of other antipsychotic medications on the pituitary gland. An aripiprazole dose of 5 mg/day is suggested.

Antipsychotic-induced amenorrhea is not a rare event among women treated for schizophrenia. Menstruation is associated with fertility, youth, attractiveness, health, and normality. Because it is often imbued with magical or spiritual significance, its absence can be experienced as distressing and can be readily misinterpreted.

In women with psychosis, the misinterpretation can lead to delusions of sex change, pseudocyesis, denial of pregnancy, and false assumptions of infertility or early menopause.

Amenorrhea is sometimes preventable, sometimes treatable, but always addressable in the sense that personal and cultural meanings can, and should, be explored within the therapeutic relationship.

Declaration of interest: The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.


1. Permission to use quotes from the site was obtained from Mr. Harry Finley, 31 August 2010.


Abraham, S., Fraser, I., Gebski, V., Knight, C., Llewellyn-Jones, D., Mira, M., et al. (1985). Menstruation,

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Ahuja, N., Moorhead, S., Lloyd, A.J., & Cole, A.J. (2008a). Antipsychotic-induced hyperprolactinemia and

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Ahuja, N., Vasudev, K., & Lloyd, A. (2008b). Hyperprolactinemia and delusion of pregnancy. Psychopathology,41,


488 M. V. Seeman

• Antipsychotic induced amenorrhoea is a common but neglected adverse effect in clinical practice. It is the earliest sign of hyperprolactinemia with prevalence rates of approximately 45% for oligomenorrhoea/amenorrhoea and 19% for galactorrhoea. Elevation of prolactin levels occurs within a few minutes to hours of treatment initiation and persists with long term treatment. Abnormalities in menstrual cycles can make a person concerned about infertility. It can lower one’s mood and affect a woman’s quality of life. Other phenomenological problems that could arise from amenorrhoea include delusions of pregnancy or pseudocyesis or denial of pregnancy and delusions of pseudo transsexualism (excessive body hair growth in hyperprolactinemia). If unaddressed, amenorrhoea can culminate in a woman suffering from schizophrenia or other psychotic disorders to decide to stop treatment.



The best way is to simply adjust the dose or type of antipsychotic. I suggest 
  1. Confirm that the cause of the hyperprolactemia is due to anti-psychotics and not due to a physical cause such as a prolactinoma, and once confirmed,
  2. Clinically assess if the person can still do well with a lower dose of the existing anti-psychotic medication and/or
  3. Switching to another antipsychotic that carries a low risk of hyper-propactinemia. E.g. Second-generation antipsychotics (SGAs), especially olanzapine, quetiapine, or even clozapine.
Best of luck, 
Dr Terence Leong
Health on the Net Foundation

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