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)


Study design Cases




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


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.

Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

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