This week we are pleased to have a guest post from Dr. Anna Glezer.  She is a perinatal psychiatrist practicing at the University of California San Francisco and the founder of Mind Body Pregnancy, a new online resource uniquely focusing on all topics related to the emotional health of women during their reproductive years.


Infertility, affecting many couples, can have a number of mental health complications like depression. The most common treatment medications can themselves also have effects on a woman’s emotional state.

Clomiphene (Clomid) and Human Menopausal Gonadotropin

One of the most commonly prescribed medications in infertility treatment is clomiphene.  Clomiphene is a medication used to treat ovulation problems, a common reason for infertility. It works by affecting a gland in the brain, the hypothalamus, leading it to trigger the pituitary gland to release the hormones LH (luteinizing hormone) and FSH (follicle stimulating hormone), both of which are essential to the ovulation cycle. Another treatment is human menopausal gonadotrophin (hMG), which also stimulates ovarian function.

Physical side effects from these medications are well known, including symptoms of hot flashes or vision changes for example, but the emotional side effects are less discussed. Women taking this medication have described feeling out of control or out of touch with reality. Others have described problems with sleep and insomnia, irritability and anxiety, and in rare cases psychosis.

A study in 2005 found that 40% of women taking clomiphene and 60% of those taking hMG experienced psychological side effects including mood swings, irritability, and feeling down. It can be a challenge to know which of these symptoms are a function of the medication, the underlying condition of infertility and its association with mood and anxiety problems, or a co-occurring mental health issue. For this reason, it is not surprising that mental health conditions in this population might be underdiagnosed.

Oral contraceptives

It may be surprising that oral contraceptives can help in the treatment of infertility, but they are used often in in vitro fertilization (IVF). These particular formulations have higher doses of progesterone, which has been associated with increased depression.

GnRH Agonists

These medications (such as leuprolide/Lupron) suppress ovarian hormones, and are therefore used commonly to treat conditions such as endometriosis. In fertility treatment, they are used in conjunction with IVF to decrease luteinizing hormone (one of the gonadal hormones). The most common psychiatric side effects of taking these medications include depression, emotional lability, and changes in libido. There are long articles detailing several theories about the mechanism behind the development of the mood symptoms related to changes in hormones such as estrogen, a topic which is beyond the scope of this article. However, the good news is that these same studies also note that the symptoms respond well to treatment, such as serotonergic antidepressant medications like sertraline.

Take-Home Points

Given that fertility treatment involves medications that modify hormones, it is not surprising that it is associated with mood changes. Given that going through fertility treatment is itself an emotionally difficult process, it is also not surprising that women going through the process are already vulnerable to these mood changes. If you are struggling with some of those common side effects such as depression, several important steps can be taken.

The first is to make sure that your treating provider – whether that is an ob/gyn or reproductive endocrinologist – is aware of this. It could mean you need a dose adjustment or a revision of the treatment plan.

Next, consider engaging with a mental health professional. That could mean a psychotherapist or it could be a psychiatrist who would be able to discuss medication treatment options. There are several recommended for women in the process of conception (such as SSRIs).

Finally, consider sharing with others in order to make sure you have a strong support system. That could mean other women going through infertility treatment. It could be your partner and family members. And it can include an online community, such as virtual groups or a resource like Mind Body Pregnancy.

Anna Glezer, MD

Selected References:

Choi, S-H. et. al. Psychological side-effects of clomiphene citrate and human menopausal gonadotrophin. Journal of Psychosomatic Obstetrics & Gynecology (2005) 26(2): 93-100.

Warmock, J.K. et. al. Depressive mood symptoms associated with ovarian suppression. Fertility andSterility. (2000) 74(5): 984-6.

Wilkins, K.M., Warnock, J.K., Serrano, E. Depressive Symptoms related to infertility and infertility treatments. Psychiatric Clin N Am 33 (2010) 309-321.

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