Critical Commentary

Although there is a paucity of information in the literature, preliminary reports suggest a promising role for NSAIDs in improving sperm quality. They are thought to stabilize lysosomal membranes, thereby partially preventing apoptosis [94, 97, 98]. Some evidence has shown that an increase in prostaglandin concentration in seminal plasma can inhibit spermatic function [98]. One study found success in treating men with iOAT and prostaglandin-F2 in seminal plasma by treating them with a NSAID called flubiprofen [97], Cinnoxicam is a lipophilic NSAID that has been shown to enhance sperm concentration, motility, and morphology [96] and even lead to higher pregnancy rates when combined with LC and LAC [54]. Its fat-soluble nature facilitates lymphatic and prostatic absorption [97, 99]. No specific biochemical study has found a mechanism by which cinnoxicam elicits its actions, although

Table 22.6 Quality assessment of oral supplementation of nonsteroidal anti-inflammatory drugs (NSAIDs)

References

Study design Cases

Dosage

Duration

Ages

Main outcome

Cavallini et al. [96]

Cavallini et al. [54]

Double-blind randomized controlled

Double-blind randomized controlled

SurgeryA; Cinnoxicam (30 mg/4d)B; Placebo (glycerine suppository lx/4d)c

Placebo (starch tablet

2 x 500 mg/d) + (glycerine suppository lx/4d)A; LC (1 x2 g/d) + LAC (500x2 mg/d) + glycerine suppository (1 x/4d)B LC (1 x2 g/d) + LAC (500x2 mg/d) + cinnoxicam suppository (1 x30 mg/d)c_

12-m intervention 34-37

6-m intervention + 3-m/6-m follow-up

28-40

t ConcentrationBab t Motility8 " t Morphology®'11 f Concentration BC(p< 0.05) t Motility BC(p<0.05) t Morphology BC(p< 0.05) t Pregnancy c(p< 0.01)

LC L-carnitine; LAC L-acetyl-carnitine; d day, mg milligram; m months 'Significant differences in sperm concentrations (pcO.OOl), but not with replicates

"Significant increases with oligoasthenospermia associated with a grade III {p<0.05), but not in those with grade IV or V varicocele it is known that NSAIDs inhibit ROS and protstaglandin synthesis. Preliminary results appear to be best following 4 months of intervention, while returning to baseline levels following therapy suspension [54, 96]. A balance is critical in regulating ROS concentration for proper sperm function; too high of concentrations inhibit sperm motility and modify sperm morphology; however, too low of concentrations downregulate sperm capacitation and acrosomal reactions [100]. For instance, one study revealed chronic treatment with NSAIDs at low doses to improve sperm quality and fertility [99], while in vitro model showed that high cinnoxicam concentrations in seminal plasma inhibit sperm motility by most likely lowering the ROS in seminal plasma to excessive low levels [97]. Additional studies are required to establish the proper dosage of cinnoxicam treatment.

Only a few minor side effects were reported—mild euphoria, mild epigastralgia, and nausea—but never resulted in therapy suspension [54]. Future randomized controlled trials should test the utility of other common NSAIDs such as aspirin and ibuprofen in the treatment of male infertility. LAC/LC + cinnoxicam suppositories reveal much potential as a reliable treatment. However, there is still not enough data to support the use of NSAIDs in the treatment of iOAT.

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