Differential Effects of Clomiphene Citrate in Women Undergoing Superovulation

Mood

Clomiphene citrate, Mood symptoms, Infertility, Superovulation, Effects of clomiphene on mood

Clomiphene citrate is commonly used for ovulation induction in women with anovulation, correction of luteal phase deficiency or for superovulation as empiric therapy for unexplained infertility. Superovulation using clomiphene, usually with intrauterine insemination, is usually regarded as first line therapy for unexplained infertility, infertility due to mild endometriosis, or infertility with mild or moderate compromise of the male factor. The side effect profile reported by some women using clomiphene citrate is similar to symptoms of premenstrual dysphoric disorder (PMDD), including tension, irritability, depressed mood, affective lability, lack of energy, difficulty concentrating, and physical symptoms such as breast tenderness, bloating, headache joint and muscle pain. Few studies have been performed to examine the relationship between clomiphene citrate and mood symptoms; however, these studies have been limited by their small sample size, potential for recall bias and lack of randomization. Moreover, the experience of infertility is dysphoric in and of itself. Therefore, a rigorous evaluation of whether, when in the cycle, and how often clomiphene is associated with mood changes is needed. Such a study would add to the body of literature on this topic in three important ways: 1) use of prospective data collection to more accurately identify commonly reported symptoms, 2) characterize the timing of symptom occurrence relative to treatment cycle, and 3) provide information relevant to planning of future studies involving targeted treatment of clomiphene citrate induced symptoms. If clomiphene use is shown to affect mood, the results would point to an important avenue for psychopharmacologic insight into relationships between mood and sex steroids. OBJECTIVES: Specific Aim #1: To identify psychological and physical symptoms experienced by women taking clomiphene citrate for superovulation in a prospective, placebo controlled trial setting. Specific Aim #2: To determine whether measures of the emotional and physical state prior to the administration of clomiphene, predict the occurrence of mood changes during the five days of clomiphene administration and in the late follicular and luteal phases of the cycle in which clomiphene was administered.

The aim of this study is to identify psychological and physical symptoms experienced by women taking clomiphene citrate for superovulation in a prospective setting. Clomiphene citrate is commonly used for ovulation induction in women with anovulation, correction of luteal phase deficiency or for superovulation as empiric therapy for unexplained infertility1. While clomiphene citrate is generally well tolerated, common side effects have been reported including vasomotor flushes, breast tenderness, pelvic discomfort, and mood swings. Visual changes, such as palenopsia are rarely reported2. The side effect profile reported by some women using clomiphene citrate is similar to symptoms of premenstrual dysphoric disorder (PMDD). Symptoms of PMDD include tension, irritability, depressed mood, affective lability, lack of energy, difficulty concentrating, and physical symptoms such as breast tenderness, bloating, headache joint and muscle pain. Several validated scales have been used to record symptom occurrences and to characterize the timing of symptom occurrence relative to the menstrual cycle3. The psychological and mood side effects of clomiphene citrate in women undergoing infertility treatment have been studied to a limited degree. One study reported mood swings in 9 out of 14 women surveyed4. Another small study found a higher frequency of irritability, mood swings, feeling down and bloating in women undergoing fertility treatment who were taking clomiphene citrate compared to no medication.

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