Results
Fifty-seven men placed on CC were identified; however, 10 men were excluded because of incomplete baseline labs. Thus, a total of 47 men were included in this analysis. Mean age and BMI were 34.5 and 30.2 years, respectively. Twenty-six men (55%) had 3 or more positive ADAM responses and 13 men (28%) had SHIM scores <21. Median follow-up time was 3.0 months (IQR: 2.3–3.7).
Effect of CC on Serum Hormone Levels
The mean baseline values and changes in hormone levels after 2 weeks of treatment with CC are shown in Table 1. There was a statistically significant improvement in both total testosterone (mean absolute improvement of 280.8 ng dl, P<0.001) and bioavailable testosterone (155.3 ng dl, P<0.001).
Effect of CC on Semen Analysis Parameters
The effect of CC on semen analysis parameters after 3 months of treatment is shown in Table 2. Mean ejaculate volume, percentage progressively motile and percentage of normal morphology were similar at 3 months vs baseline. However, mean total motile count and concentration increased to 90.9 and 72.5 millions ml at 3 months from 59.7 and 50.7 millions ml at baseline, respectively, although these findings were not significant (P=0.09, 0.09).
Correlation of Baseline Demographics and Hormones Levels With Improvement in Bioavailable Testosterone on CC
On unadjusted and age-adjusted regression analysis, age, BMI, longitudinal testis axis, baseline FSH, LH and estradiol did not significantly correlate with improvement in bioavailable testosterone at 2 weeks (Table 3). Additionally, three or more positive ADAM responses, SHIM score <21 and varicocele presence at baseline was not associated with bioavailable testosterone levels following 2 weeks of CC (P=0.85, 0.68, 0.72, respectively).
Adverse Effects of CC
Adverse effects were reported in five (11%) of patients. Two patients had a paradoxical decrease in total testosterone at 2 weeks and were switched to hCG (absolute decrease of 11.0 and 57.3 ng dl). Both patients had an adequate response to hCG treatment after 2 weeks, with an increase of 655 and 82 ng dl in total testosterone, respectively, when compared with their postclomiphene values. An additional two patients discontinued CC at 3 months: one because of increased fatigue and mood symptoms and one who experienced a delayed decline in total testosterone compared with total testosterone at 2 weeks (absolute decrease of 222.0 ng dl). No patients experienced a paradoxical decrease in total motile count or concentration while on CC after 3 months.