Pharmacokinetics of non-steroidal anti-inflammatory drugs in male rabbits after acute and chronic administration and effect of chronic treatment on seminal prostaglandins, sperm quality and fertility

Löscher, Wolfgang; Lüttgenau, H.; Schlegel, Werner; Kruger, Sally R.

doi:10.1530/jrf.0.0820353

Cited by 14 publications

(7 citation statements)

References 29 publications

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“…[8687] Treatment with low-dose NSAIDs was shown to improve sperm quality and fertility in an animal model. [88] Interestingly, carnitine administration was reported to promote the accumulation of prostaglandin E2 in seminal fluid. [89] Therefore, the concomitant administration of NSAIDs with carnitines may have a complementary mechanism that facilitates the positive effects of carnitine therapy while counteracting excess prostaglandin production.…”

Section: Non-steroidal Anti-inflammatory Drugsmentioning

confidence: 99%

“…However, a certain level of prostaglandins and oxidative stress is required for physiologic sperm functioning. Although long-term treatment with NSAIDs at low doses has been associated with improved sperm quality and fertility,[88] in vitro experiments have illustrated that higher dosage of NSAIDs may inhibit sperm motility. [90] NSAIDs administered via a suppository are thought to exert a more pronounced and direct effect on seminal plasma due to rectal-prostatic lymphatic pathways.…”

Section: Non-steroidal Anti-inflammatory Drugsmentioning

confidence: 99%

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Oxidative stress and antioxidants for idiopathic oligoasthenoteratospermia: Is it justified?

Agarwal¹,

Sekhon²

2011

Indian J Urol

120

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Oxidative stress contributes to defective spermatogenesis and the poor quality of sperm associated with idiopathic male factor infertility. The aim of this study was to review the current literature on the effects of various types of antioxidant supplements in patients to improve fertilization and pregnancy rates in subfertile males with idiopathic oligoasthenoteratozoospermia (iOAT). Review of recent publications through PubMed and the Cochrane database. Oxidative stress is implicated in impaired spermatogenesis leading to the poor semen parameters and increased DNA damage and apoptosis in iOAT. Strategies to modulate the level of oxidative stress within the male reproductive tract include the use of oral antioxidant compounds to reinforce the body's defence against oxidative damage. In our evaluation, carnitines were considered the most established pharmacotherapeutic agent to treat iOAT, as evidence and data concerning carnitine supplementation have been shown to be most consistent and relevant to the population of interest. Other therapies, such as combined vitamin E and C therapy, are still considered controversial as vitamin C can act as a pro-oxidant in certain instances and the results of randomized controlled trials have failed to show significant benefit to sperm parameters and pregnancy rates. There is a need for further investigation with randomized controlled studies to confirm the efficacy and safety of antioxidant supplementation in the medical treatment of idiopathic male infertility as well as the need to determine the dosage required to improve semen parameters, fertilization rates and pregnancy outcomes in iOAT.

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Section: Non-steroidal Anti-inflammatory Drugsmentioning

confidence: 99%

Section: Non-steroidal Anti-inflammatory Drugsmentioning

confidence: 99%

Oxidative stress and antioxidants for idiopathic oligoasthenoteratospermia: Is it justified?

Agarwal¹,

Sekhon²

2011

Indian J Urol

120

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“…Hydrophilic NSAIDs were less active than C, whose lipophilia facilitate absorption [176]. An animal model showed that chronic treatment with NSAIDs at low doses improved sperm quality and fertility [178]. Carnitine administration was found to increase E2 prostaglandin concentration [179], which affects sperm count [180,181].…”

Section: Therapymentioning

confidence: 99%

Male idiopathic oligoasthenoteratozoospermia

Cavallini¹

2006

Asian J Andrology

141

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Idiopathic oligoasthenoteratozoospermia (iOAT) affects approximately 30% of all infertile men. This mini-review discussed recent data in this field. Age, non-inflammatory functional alterations in post-testicular organs, infective agents (Chlamydia trachomatis, herpes virus and adeno-associated viruses), alterations in gamete genome, mitochondrial alterations, environmental pollutants and "subtle" hormonal alterations are all considered possible causes of iOAT. Increase of reactive oxygen species in tubules and in seminal plasma and of apoptosis are reputed to affect sperm concentration, motility and morphology. iOAT is commonly diagnosed by exclusion, nevertheless spectral traces of the main testicular artery may be used as a diagnostic tool for iOAT. The following can be considered therapies for iOAT: 1) tamoxifen citrate (20 mg/d) + testosterone undecanoate (120 mg/d) (pregnancy rate per couple/month [prcm]: 3.8%); 2) folic acid (66 mg/d) + zinc sulfate (5 mg/d); 3) L-carnitine (2 g/d) alone or in combination with acetyl-L-carnitine (1 g/d) (prcm: 2.3%); and 4) both carnitines = one 30 mg cinnoxicam suppository every 4 days (prcm: 8.5%). Alpha-blocking drugs improved sperm concentration but not morphology, motility or pregnancy rate. Tranilast (300 mg/d) increased sperm parameters and pregnancy rates in an initial uncontrolled study. Its efficacy on sperm concentration (but not on sperm motility, morphology or prcm) was confirmed in subsequent published reports. The efficacy of tamoxifen + testosterone undecanoate, tamoxifen alone, and recombinant follicle-stimulating hormone is still a matter for discussion.

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“…ROS concentration is critical in regulating sperm function; if too high it inhibits sperm motility and modifies the morphology to the point of producing McLeod stress patterns [10], but too low and it down-regulates capacitation and acrosomal reactions [23]. Confirming this kind of 'spot therapy', experimental models showed that chronic treatment with NSAIDs at low doses improved sperm quality and fertility [24], and in vitro experiments showed that a high cinnoxicam concentration in seminal plasma inhibited sperm motility [25].…”

Section: Discussionmentioning

confidence: 99%

Medical therapy of oligoasthenospermia associated with left varicocele

et al. 2003

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The authors from Ferrara show that a NSAID has a role in patients who have oligoasthenospermia associated with a left‐sided varicocele, although not in every case. Peyronie's disease is discussed in two papers; in the first of these, the authors make the case for histopathological diagnosis by drawing the reader's attention to the possible presence of penile epithelioid sarcoma. In the second paper, attention is drawn to the possibility of using a combination of vitamin E and colchicine in the early stages of the condition. Objective To ascertain whether a nonsteroidal anti‐inflammatory drug (cinnoxicam) or surgical varicocelectomy are suitable therapies for oligoasthenospermia associated with varicocele. Patients and methods Patients who were oligoasthenospermic and had a varicocele were blindly randomized into three groups and the varicocele graded using echo‐colour Doppler ultrasonography. In group 1, seven men had grade V, four grade IV and 30 grade III varicoceles; in group 2 eight had grade V, 10 grade IV and 43 grade III; in group 3 six had grade V, eight grade IV and 40 grade III. Group 1 underwent surgery, group 2 received cinnoxicam (one 30 mg suppository every 4 days for 12 months) and group 3 received a placebo (one glycerine suppository every 4 days for 12 months). Sperm was analysed at intervals to follow the response in the three groups, and any side‐effects considered. Results Surgery significantly increased sperm values in men with grade III–V varicocele within 4 months, the highest values being obtained at 8 and 12 months. Cinnoxicam significantly improved sperm quality after 2 months in men with grade III varicocele, but the results were best at 4 months and stable at 12 months; stopping therapy caused a decline to the baseline values. Cinnoxicam did not change the sperm quality of men with grade IV or V varicocele. The placebo was inactive, and there were no side‐effects of active treatment. Conclusions Cinnoxicam is a safe and reliable therapeutic option for men with oligoasthenospermia associated with a grade III varicocele, but surgery is better for those with grade II, IV and V.

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Pharmacokinetics of non-steroidal anti-inflammatory drugs in male rabbits after acute and chronic administration and effect of chronic treatment on seminal prostaglandins, sperm quality and fertility

Cited by 14 publications

References 29 publications

Oxidative stress and antioxidants for idiopathic oligoasthenoteratospermia: Is it justified?

Oxidative stress and antioxidants for idiopathic oligoasthenoteratospermia: Is it justified?

Male idiopathic oligoasthenoteratozoospermia

Medical therapy of oligoasthenospermia associated with left varicocele

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