In another animal study, the fertility of 10 male rats (with an average weight of 275 g) was examined after 60 days of administration of fluoxetine (200 mg/kg) compared to that of 10 control rats (with an average weight of 267 g) receiving placebo (Bataineh & Daradka, 2007 ). The study showed that after 60 days of treatment the rats treated with fluoxetine showed significantly lower weight of their sex organs compared to the placebo treated rats [testes (869 ± 9.83 vs. 925 ± 9.83 mg/100 g body weight, p < 0.001), epididymides (312 ± 3.81 vs. 395 ± 8.62, p < 0.001), seminal vesicle (361 ± 9.37 vs. 404.58 ± 5.5, p < 0.001), ventral prostate (169 ± 5.38 vs. 215 ± 3.01, p < 0.001) and vas deferens (87 ± 1.78 vs. 64 ± 0.66, p < 0.05)]. Furthermore, they showed significantly lower sperm motility (9.23 ± 0.33% vs. 74.1 ± 1.94%, p < 0.001), sperm density in testes (1.12 ± 0.65 vs. 4.75 ± 0.47 mio/L, p < 0.001) and in cauda (4.4 ± 1.66 vs. 56.0 ± 1.94, p < 0.001), number of germinal and interstitial cells in testes, as well as significantly lower serum concentration of follicle stimulating hormone (FSH) and testosterone. Each male rat was placed in an individual cage with two virgin untreated female rats. As a collective measure of fertility the number of pregnant female rats was measured for both fluoxetine‐treated and placebo‐treated rats. The fluoxetine‐treated males gave significantly fewer pregnancies compared to the placebo‐treated (40% vs. 90%, p < 0.05 [chi‐squared test]), a lower number of implantations (5.36 ± 2.83 vs. 9.63 ± 2.66, p < 0.001) and a lower number of viable fetuses (5.25 ± 1.67 vs. 9.37 ± 1.16, p < 0.001).

Alzahrani examined three groups of five male rats given fluoxetine orally in three different doses (2.6, 7.8 and 13.0 mg/kg body weight) plus a fourth negative control group (Alzahrani, 2012 ). They were treated for 5 days and sacrificed 24 h after the last treatment and left for 35 days from the first treatment for analysis of sperm shape abnormalities. The results for all three doses were a significantly lower sperm count, significantly lower motility and a significantly higher percentage of abnormal sperm heads in the treated groups compared to the control subjects. A dose–effect relationship was noted for all three parameters with the strongest response in the group treated with the highest dose. Unfortunately no examination of the semen was carried out before treatment.

An in vitro study (Kumar et al ., 2006 ) examined semen samples from three different donors (it is not disclosed whether they had any psychiatric disorders). They added five different SSRIs (paroxetine, fluoxetine, sertraline, citalopram and fluvoxamine) as well as serotonin in varying doses to the semen samples. The minimum effective spermicidal concentration (MEC) is defined as the minimum dose where 100% of the spermatozoa become immotile in 20 sec; and ED 50 is defined as the dose that immobilizes 50% of the spermatozoa. These values were determined from a motility–concentration curve. All of the tested SSRIs showed to possess spermicidal activities with MEC ranging from 0.1 to 0.05%. The ED 50 values for these SSRI antidepressants ranged from 0.00007 to 0.04%. In comparison, nonoxynol‐9 (N‐9), which was earlier used as an anticonceptional spermicide, was examined. This compound has an MEC of 0.05%, equivalent to that of the most effective spermicidal SSRI, fluoxetine. Serotonin showed no spermicidal activity.

Research shows that anxiety disorders such as panic disorder, social anxiety disorder and obsessive–compulsive disorder are associated with reduced sexual activity (Figueira et al ., 2001 ; Kendurkar & Kaur, 2008 ; Aksoy et al ., 2012 ). Men with social anxiety disorder show increased incidence of premature ejaculation (Corretti et al ., 2006 ). Psychosocial stress also seems to affect semen parameters. Stress as a primary and independent factor of male infertility is difficult to isolate from other risk factors, because there is a tendency with persons suffering from depression and anxiety to have problems with obesity, alcohol and tobacco as well (Hall & Burt, 2012 ). It has been demonstrated that all of these factors affect semen parameters (Aagaard & Hansen, 2007 ).

Depression and anxiety may cause sexual dysfunction. Research has been carried out on depressed men. Reduced libido is the most common symptom, but erectile dysfunction and delayed or inhibited ejaculation are also seen (Williams & Reynolds, 2006 ; Baldwin & Foong, 2013 ; Fabre et al ., 2013 ; Gelenberg et al ., 2013 ). These findings are documented in depressed men before the start of treatment with antidepressant medications, and the incidence of sexual symptoms seems associated to the severity of the depression (Ishak et al ., 2013 ).

SSRIs and sexuality

Several studies have shown that all of the SSRIs can cause sexual side effects in both males and females. The incidence is however highly varying in the different studies (Gelenberg et al., 2013). In men, reduced libido, erectile dysfunction and inhibited ejaculation are seen (Balon, 2006). The inhibitory effect of SSRIs on ejaculation is so strong that it can be used as a treatment for premature ejaculation (Burton & Liday, 2011; Porst, 2011). The sexual side effects are difficult to distinguish from the sexual symptoms related to depression. Ishak et al. (2013) found that the incidence of sexual problems after treatment was highest among the depressed patients, who did not benefit from the treatment with citalopram. Furthermore, the depressive patients who had achieved remission had fewer sexual problems than before the treatment, likely explained by the bettering of the depression‐related sexual symptoms. Gelenberg et al. (2013) found that the risk of sexual side effects of the treatment with fluoxetine and venlafaxine was highest for patients with recurring depression (who had no sexual problems before the treatment) and for patients who had no effect of the antidepressant. The relationship between depression, SSRIs and sexual dysfunction is thus complicated and not fully explored.

Case reports on SSRIs and semen quality In a case report (Tanrikut & Schlegel, 2007), the semen quality of two men treated for depression with SSRIs was described. The patients presented with a temporal association between use of SSRIs and impaired semen quality. The first patient was a 44‐year‐old man treated for depression with citalopram, who was referred to the clinic with a 7‐month history of primary infertility. There is no information on the duration of the medical treatment. The physical examinations, scrotal ultrasonography and blood levels of hormones were all normal and antisperm antibodies could not be detected. His initial semen analyses while having taken citalopram showed very low sperm count and 1% motility. One month after discontinuation of the citalopram treatment, semen analysis showed normal values. Shortly thereafter he was treated with bupropion for his depression, and a semen analysis showed decreased sperm concentration to 21 million/mL and 10% motility. The lower reference limit for sperm concentration is 15 million spermatozoa per mL (5th centile, 95% CI 12–16 × 106) (Department of Reproductive Health and Research, WHO, 2010). One year after, while still taking bupropion, sperm chromatin assay showed DNA fragmentation index of 76%. One month after discontinuation of bupropion, a new semen analysis showed 75% motility and a normal sperm concentration (41 million/mL). After 2 months, the analysis showed normal motility and concentration. Another patient, a 35‐year‐old man referred for primary infertility, had been taking sertraline for depression for 5 years. His physical examination and blood tests were normal. The primary semen analyses while taking sertraline showed decreased sperm concentration (20.000/mL) and no motile spermatozoa. A repeat semen analysis immediately after discontinuation of sertraline showed similar results, but after 3 months discontinuation he presented with normal parameters and 40 million/mL motile spermatozoa in his ejaculate. Shortly after he started with bupropion. Venlafaxine treatment was later added, and repeat analyses during this period of treatment showed no motile sperm. One month after discontinuation of all medications the analyses returned to normal (Ginsberg, 2007; Tanrikut & Schlegel, 2007). Another case report described a 30‐year‐old man suffering from anxiety and depression who had been treated with 40 mg citalopram during 3 years and was referred to examination for infertility (Elnazer & Baldwin, 2014). The semen analysis showed reduced sperm concentration (11 million/mL), 25% motility and abnormal morphology of 99%. The patient chose to discontinue the treatment with citalopram and after 4 months he showed an improved semen quality with a sperm concentration of 16 million/mL and 60% motility, but with a persisting abnormal morphology of 98%. Due to increasing anxiety symptoms and sleep problems, treatment with agomelatine 50 mg/day (a melatonin agonist with inhibitory effect on serotonin receptor 5HT2C) was initiated 20 months after the discontinuation of citalopram. Three months after the initiation of agomelatine treatment, the semen analyses showed normal sperm concentration of 15 million/mL, 62% motility and abnormal morphology 95%. It is considered likely that there was causality between the treatment with citalopram and the reduced semen quality. An ultrasound found evidence of a small unilateral subclinical varicocoele that was considered to be clinically insignificant.