Ibuprofen linked to male infertility, study says

Ibuprofen has a negative impact on the testicles of young men, a ...

Posted: Jan 9, 2018 9:00 AM
Updated: Jan 9, 2018 9:00 AM

Ibuprofen has a negative impact on the testicles of young men, a study published Monday in the journal Proceedings of the National Academy of Sciences found. When taking ibuprofen in doses commonly used by athletes, a small sample of young men developed a hormonal condition that typically begins, if at all, during middle age. This condition is linked to reduced fertility.

Advil and Motrin are two brand names for ibuprofen, an over-the-counter pain reliever. CNN has contacted Pfizer and Johnson & Johnson, the makers of both brands, for comment.

Aspirin, acetaminophen (paracetamol) and ibuprofen disrupt male hormones

Taken in high daily doses, ibuprofen induced compensated hypogonadism in young men

The Consumer Healthcare Products Association, a trade group that represents manufacturers of over-the-counter medications and supplements, "supports and encourages continued research and promotes ongoing consumer education to help ensure safe use of OTC medicines," said Mike Tringale, a spokesman for the association. "The safety and efficacy of active ingredients in these products has been well documented and supported by decades of scientific study and real-world use."

The new study is a continuation of research that began with pregnant women, explained Bernard J-gou, co-author and director of the Institute of Research in Environmental and Occupational Health in France.

J-gou and a team of French and Danish researchers had been exploring the health effects when a mother-to-be took any one of three mild pain relievers found in medicine chests around the globe: aspirin, acetaminophen (also known as paracetamol and sold under the brand name Tylenol) and ibuprofen.

Their early experiments, published in several papers, showed that when taken during pregnancy, all three of these mild medicines affected the testicles of male babies.

Testicles and testosterone

Testicles not only produce sperm, they secrete testosterone, the primary male sex hormone.

All three drugs then are "anti-androgenic," meaning they disrupt male hormones, explained David M. Kristensen, study co-author and a senior scientist in the Department of Neurology at Copenhagen University Hospital.

The three drugs even increased the likelihood that male babies would be born with congenital malformations, Kristensen noted.

Tringale noted that pregnant and nursing women should always ask a health professional before using medicines.

Knowing this, "we wondered what would happen in the adult," he said. They focused their investigation on ibuprofen, which had the strongest effects.

A non-steroidal anti-inflammatory drug, ibuprofen is often taken by athletes, including Olympians and professional soccer players for example, before an event to prevent pain, J-gou said. Are there health consequences for the athletes who routinely use this NSAID?

The research team recruited 31 male volunteers between the ages of 18 and 35. Of these, 14 were given a daily dosage of ibuprofen that many professional and amateur athletes take: 600 milligrams twice a day, explained J-gou. (This 1200-mg-per-day dose is the maximum limit as directed by the labels of generic ibuprofen-products.) The remaining 17 volunteers were given a placebo.

For the men taking ibuprofen, within 14 days, their luteinizing hormones -- which are secreted by the pituitary gland and stimulate the testicles to produce testosterone -- became coordinated with the level of ibuprofen circulating in their blood. At the same time, the ratio of testosterone to luteinizing hormones decreased, a sign of dysfunctional testicles.

This hormonal imbalance produced compensated hypogonadism, a condition associated with impaired fertility, depression and increased risk for cardiovascular events, including heart failure and stroke.

For the small group of young study participants who used ibuprofen for only a short time, "it is sure that these effects are reversible," J-gou said. However, it's unknown whether the health effects of long-term ibuprofen use are reversible, he said.

After this randomized, controlled clinical trial, the research team experimented with "little bits of human testes" provided by organ donors and then conducted test tube experiments on the endocrine cells, called Leydig and Sertoli cells, which produce testosterone, explained J-gou.

The point was to articulate "in vivo, ex vivo and in vitro" -- in the living body, outside the living body and in the test tube -- that ibuprofen has a direct effect on the testicles and so testosterone.

"We wanted to understand what happened after exposure (to ibuprofen) going from the global human physiology over to the specific organ (the testis) down to the endocrine cells producing testosterone," Kristensen said.

More than idle curiosity prompted such an extensive investigation.

Questions around male fertility

The World Health Organization estimates that one in every four couples of reproductive age in developing countries experiences childlessness despite five years of attempting pregnancy.

A separate study estimated that more than 45 million couples,-or about 15% of all couples worldwide, were infertile in 2010, while another unrelated study suggested that men were solely responsible for up to 30% and contribute up to 50% of cases overall.

Meanwhile, a recent-analysis published in the journal-Human Reproduction Update found that sperm counts of men in North America, Europe, Australia and New Zealand-are plunging. Researchers recorded a 52% decline in sperm concentration and a 59% decline in total sperm count over a nearly 40-year period ending in 2011.

Erma Z. Drobnis, an associate professional practice professor of reproductive medicine and fertility at the University of Missouri, Columbia, noted that most drugs are not evaluated for their effects on human male fertility before marketing.-Drobnis, who was not involved in the new study, has done extensive research into sperm biology and fertility.

"There is evidence that some medications are particularly harmful to the male reproductive system, including testosterone, opioids, antidepressants, antipsychotics, immune modulators and even the over-the-counter antacid cimetidine (Tagamet)," she said. "However, prescribing providers rarely mention-these adverse effects with patients when prescribing these medications.

She believes the new study, though small, is "important" because ibuprofen is among the most commonly used medications.

Though the new research indicates that ibuprofen disrupts the reproductive hormones in healthy young men, she thinks it's possible there's an even greater negative effect in men with low fertility.-The other OTC drugs concerning for potential fathers are cimetidine and acetaminophen. She recommends that men who are planning to father a child avoid drugs for several months.

"Larger clinical trials are warranted," she said. "This is timely work that should raise awareness of medication effects on men and potentially their offspring."

J-gou agrees that more study is needed to answer many questions, including whether ibuprofen's effects on male hormones are seen at low doses and whether long-term effects are reversible.

"But the alarm has been raised now," he said. "if this serves to remind people that we are really dealing with medical drugs -- not with things which are not dangerous -- this would be a good thing."

"We need to remember that it is a pharmaceutical compound that helps a lot of people worldwide," Kristensen said. He noted, though, that of the three mild analgesics examined, ibuprofen had "the broadest endocrine-disturbing properties identified so far in men."

Indiana Coronavirus Cases

(Widget updates once daily at 8 p.m. ET)

Confirmed Cases: 32078

Reported Deaths: 2004
CountyConfirmedDeaths
Marion9268539
Lake3320168
Cass15826
Allen130966
St. Joseph120534
Hendricks113067
Hamilton111592
Johnson1086104
Elkhart105728
Madison58258
Porter49021
Bartholomew48133
Clark46138
LaPorte41522
Tippecanoe3753
Jackson3671
Howard36519
Delaware35735
Hancock32127
Shelby31521
Floyd31438
Boone28835
Morgan26224
Vanderburgh2482
Montgomery23117
White2268
Decatur22431
Clinton2221
Grant19121
Noble18921
Harrison18721
Dubois1852
Greene16724
Warrick16426
Dearborn16421
Henry1619
Monroe16011
Vigo1477
Lawrence14423
Miami1391
Putnam1337
Jennings1274
Orange12422
Scott1183
Ripley1126
Franklin1068
Kosciusko941
Carroll922
Daviess8216
Steuben802
Marshall761
Newton7410
Wabash722
Wayne715
Fayette684
LaGrange602
Jasper581
Washington521
Fulton471
Rush452
Jay440
Randolph433
Jefferson411
Whitley402
Pulaski390
Clay391
Owen341
Brown331
Sullivan321
Starke313
DeKalb311
Perry260
Huntington262
Knox250
Tipton251
Benton250
Wells240
Crawford230
Blackford211
Switzerland190
Fountain182
Spencer171
Posey170
Parke170
Gibson142
Ohio130
Warren121
Adams121
Vermillion90
Martin90
Union80
Pike60
Unassigned0154

Illinois Coronavirus Cases

(Widget updates once daily at 7 p.m. CT)

Confirmed Cases: 113195

Reported Deaths: 4923
CountyConfirmedDeaths
Cook738193354
Lake7767250
DuPage7290340
Kane5866153
Will5238258
Winnebago199351
McHenry145268
St. Clair101773
Kankakee80242
Kendall72719
Rock Island63922
Champaign5697
Madison54056
Boone40716
Sangamon33226
DeKalb3313
Randolph2593
Jackson22810
McLean21210
Stephenson1952
Ogle1922
Macon18819
Peoria1858
Clinton17816
Out of IL1771
Union1417
LaSalle14013
Whiteside13310
Iroquois1314
Unassigned1200
Coles1159
Warren1140
Jefferson10116
Knox950
Monroe9211
Grundy892
McDonough835
Lee761
Tazewell683
Cass670
Henry670
Williamson541
Marion500
Jasper457
Adams441
Macoupin421
Perry410
Pulaski400
Montgomery391
Vermilion391
Morgan341
Christian334
Livingston312
Douglas280
Jo Daviess270
Fayette203
Ford201
Jersey201
Washington180
Woodford182
Mason170
Menard170
Shelby161
Bureau151
Hancock150
Mercer150
Carroll132
Franklin120
Piatt120
Crawford110
Fulton110
Bond101
Brown100
Clark100
Cumberland100
Logan100
Moultrie100
Schuyler100
Wayne91
Alexander80
Henderson80
Johnson70
Massac70
Saline70
Effingham61
Greene50
Marshall50
De Witt40
Lawrence40
Richland30
Stark30
Clay20
Edwards20
Gallatin20
Hamilton20
Wabash20
White20
Calhoun10
Hardin10
Pike10
Pope10
Putnam10
Edgar00
Terre Haute
Few Clouds
69° wxIcon
Hi: 87° Lo: 68°
Feels Like: 69°
Robinson
Clear
67° wxIcon
Hi: 86° Lo: 66°
Feels Like: 67°
Indianapolis
Scattered Clouds
71° wxIcon
Hi: 87° Lo: 68°
Feels Like: 71°
Rockville
Clear
65° wxIcon
Hi: 85° Lo: 67°
Feels Like: 65°
Casey
Clear
68° wxIcon
Hi: 83° Lo: 66°
Feels Like: 68°
Brazil
Few Clouds
69° wxIcon
Hi: 85° Lo: 67°
Feels Like: 69°
Marshall
Few Clouds
69° wxIcon
Hi: 87° Lo: 67°
Feels Like: 69°
No Major Changes
WTHI Planner
WTHI Temps
WTHI Radar

WTHI Events