| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
The publication by Luboshitzky et al
(2002) concerning the effects
of melatonin on human sperm quality deserves strong critique for a number of
reasons. The authors performed a double-blind crossover study during which
healthy volunteers were given either melatonin (3 mg) or a placebo for 3
months each, while between the phases, a washout phase of 2 weeks was
included. At the beginning and end of the 2 phases, a total of 11 parameters
(sperm and endocrine) were measured and, again, 3 and 6 months after the end
of the study. According to the results (!!), volunteers were divided into 2
groups, responders (n = 2) and nonresponders (n = 6). The criterion was that
both sperm concentration and sperm motility "dropped during the
melatonin treatment period." Both of these men belonged to the group to
which melatonin was given in the second treatment period. The title and the
conclusions of this paper are simply not justified by the data for the
following reasons:
|
In summary, I see no evidence whatsoever for the conclusion that melatonin impairs sperm parameters in healthy men. It rather appears that an expected result influenced the way the data were handled.
References
Chen Z, Toth T, Godfrey-Bailey L, Mercedat N, Schiff I, Hauser R.
Seasonal variation and age-related changes in human semen parameters.
J Androl. 2003;24: 226
–231.
Juneja HS, Karanth S, Dutt A, Parte P, Meherjee P. Diurnal variations and temporal coupling of bioactive and immunoactive luteinizing hormone, prolactin, testosterone and 17-beta-estradiol in adult men. Horm Res. 1991;35: 89 –94.[Medline]
Lewy AJ, Bauer VK, Ahmed S, Thomas KH, Cutler NL, Singer CM, Moffit MT, Sack RL. The human phase response curve (PRC) to melatonin is about 12 hours out of phase with the PRC to light. Chronobiol Int. 1998;15: 71 –83.[Medline]
Luboshitzky R, Shen-Orr Z, Nave R, Lavi S, Lavie P. Melatonin
administration alters semen quality in healthy men. J
Androl. 2002;23: 572
–578.
We appreciate the comments of Lerchl
(2004) regarding the effect of
exogenous melatonin on sperm quality in normal men
(Luboshitzky et al, 2002). In
this study, we examined the possible effect of melatonin on semen
concentration, motility, and morphology in 8 healthy young men. Since we did
not study fertility in the general sense, we performed one semen analysis at
baseline. We fully agree that 2 semen samples are indicated for the initial
evaluation of fertility. In our study, we defined a subject as a responder if
his sperm concentration and motility dropped during the melatonin treatment
period. The individual results of semen analysis were given in our study in
Figure 1. In 2 men, we found decreases in sperm concentration and motility
that were below the normal range (WHO,
1993). Since the sequence of medications in these subjects was a
placebo followed by melatonin, we concluded that the decrease in semen quality
was associated with melatonin administration. We also observed an increase in
sperm concentration in 3 subjects during melatonin administration. These
counts were within the reference range and were not associated with similar
changes in sperm motility. We attributed these changes to the well-known
variations between samples that exist in the same individual
(WHO, 1993). The data presented
by Lerchl in the figure describe the average (±SEM) values for sperm
concentration for all 8 volunteers examined. It is obvious from our study
that, as a group, no trend is seen during melatonin
treatment.
|
We also determined fasting serum gonadotropins and testosterone and estradiol levels. Although testosterone is secreted in a diurnal fashion (Luboshitzky et al, 2003), a single time point in the morning is sufficient for the assessment of the pituitary-gonadal axis function in men if hormone levels are within the reference range. A recent study has demonstrated that sperm parameters vary with season and advanced age (Chen et al, 2003). These results do not contradict our findings, as we conducted our study between October and May, in a different time zone and in young men.
We fully agree with the comment that exogenous melatonin influences the diurnal rhythm of the endogenous hormone. In fact, when suitably timed, melatonin administration appears to be beneficial in alleviating symptoms of circadian-based sleep disorders, shift work, jet lag, and delayed sleep phase syndrome as well as a sleep-promoting agent in elderly insomniacs (Zhdanova and Wurtman, 1997; Sack et al, 2000).
Taken together, the data suggest that exogenous melatonin alters semen quality in some men. Melatonin action at the hypothalamic-pituitary level is less likely in view of unaltered serum gonadotropin levels in our study. A direct inhibitory effect of melatonin on testicular and epididymal aromatase resulting in an altered androgen/estrogen milieu and, consequently, decreased sperm concentration and motility is a more plausible possibility. This is supported by previous observations that low sperm production is associated with low seminal plasma aromatase activity and higher melatonin levels (Yie et al, 1991). Also, in frogs, melatonin has a direct inhibitory effect on the basal- and estradiol-stimulated mitotic activity of primary spermatogonia in the testis (d'Istria et al, 2003).
In summary, the results of our preliminary study suggest that melatonin decreases sperm counts and motility to subnormal levels in some healthy young men. When considering the long-term use of melatonin, extra precautions should be taken, especially in men with low normal sperm counts.
References
Chen Z, Toth T, Godfrey-Bailey L, Mercedat N, Schiff I, Hauser R. Seasonal variation and age-related changes in human semen. J Androl. 2003;24: 226 –231.
d'Istria M, Palmiero C, Seino I, Izzo G, Minucci S. Inhibition of the basal and oestradiol-stimulated mitotic activity of primary spermatogonia by melatonin in the testis of the frog, Rana esculenta, in vivo and in vitro. Reproduction. 2003; 126: 83 –90.[Abstract]
Lerchl A. Letter to the editor. J Androl. 2004; 25: 185
.
Luboshitzky R, Shen-Orr Z, Herer P. Middle-aged men secrete less
testosterone at night than young healthy men. J Clin Endocrinol
Metab. 2003;88: 3160
–3166.
Luboshitzky R, Shen-Orr Z, Nave R, Lavi S, Lavie P. Melatonin administration alters semen quality in healthy men. J Androl. 2002;23: 572 –578.
Sack RL, Brandes RW, Kendall AR, Lewy AJ. Entrainment by free-running circadian rhythms by melatonin in blind people. N Engl J Med. 2000;343: 1070 –1077.[Medline]
World Health Organization. WHO Laboratory Manual for the Examination of Human Semen and Semen–Cervical Mucus Interactions. New York, NY: Cambridge University Press; 1993 .
Yie SM, Daya S, Brown GM, Deys L, Younglai EV. Melatonin and aromatase stimulating activity of human seminal plasma. Andrologia. 1991; 23: 227 –231.[Medline]
Zhdanova IV, Wurtman RJ. Efficacy of melatonin as a sleep-promoting agent. J Biol Rhythms. 1997; 12: 644 –650.
This article has been cited by other articles:
 |
|
 |
|
  A. Lerchl and R. Luboshitzky Melatonin Administration Alters Semen Quality in Normal Men J Androl, March 1, 2004; 25(2): 185 - 187. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
