A Pilot Study Associating Urinary Concentrations of Phthalate Metabolites and Semen Quality

Figures & data

Participant Demographics.

Parameter	Study	Population
		%
Mean age	34.8	–
Racial group
Caucasian	35	77.8
African American	5	11.1
Other race	5	11.1
Education
High school or less	9	20.0
Some post-secondary	16	36.6
At least 4 years of college	20	44.4
Annual income
< $15,000	1	2.27
$15,000–<$45,000	10	22.7
$45,000–<90,000	16	36.4
$90,000 and greater	15	34.1
Not reported	3	6.67
Mean BMI	29.0	–
Smoking status
Current smoker	11	24.4
Former smoker	11	24.4
Lifetime nonsmoker	23	51.1
Alcohol servings/week
None	11	24.5
0.24–3	13	28.9
>3–7.5	10	22.2
>7.5	11	24.4
Sperm parameters (median)
Concentration	42.2	–
Motility	55.0	–
% normal forms	2.0	–
Sperm parameters (mean)
Concentration	50.2	–
Motility	53.5	–
% normal forms	3.2	–

Distribution of Urinary Phthalate Metabolite Levels.

Phthalate metabolites	Min.	5th	25th	50th	75th	95th	Max.	Geo. mean (μ/L)
MMP	0.0	0.0	1.6	2.4	4.5	14.7	60.4	1.1
MEP	14.8	22.1	43.3	108.0	292.4	1,180.0	2,916.7	121.9
MBP	5.5	7.4	16.0	24.7	44.3	144.5	198.0	26.9
MiBP	1.1	2.3	3.7	5.8	10.0	17.9	61.9	6.3
MBzP	3.8	4.7	11.6	17.4	31.3	166.6	214.1	20.0
MEHP	1.5	2.5	4.6	10.1	22.1	85.4	334.3	11.5
MEOHP	1.8	7.6	20.1	37.6	79.3	263.8	670.0	39.1
MEHHP	3.6	13.9	32.7	56.6	137.1	507.0	1,122.2	66.1
MCPP	0.0	0.0	2.6	4.6	8.3	20.5	40.8	2.5

Spearman's Rank Correlations of Specific Gravity-Adjusted Phthalate Metabolite Levels. P-values are Shown Below the Correlation Coefficients.

	MBzP	MCPP	MEP	MMP	MBP	MiBP	MEHHP	MEHP	MEOHP
MBzP	1.00	0.61***	0.27	0.31	0.50***	0.26	0.33	0.18	0.29
MCPP		1.00	0.07	−0.01	0.34*	0.18	0.34*	0.16	0.33*
MEP			1.00	0.50***	0.46**	0.42**	0.19	0.26	0.17
MMP				1.00	0.49***	0.34*	0.21	0.22	0.23
MBP					1.00	0.52***	0.33*	0.25	0.32*
MiBP						1.00	0.22	0.14	0.24
MEHHP							1.00	0.81***	0.99***
MEHP								1.00	0.81***
MEOHP									1.00

Bolded values are significant: *denotes p≤0.05, **denotes p≤0.01, ***denotes p≤0.001.

Odds Ratios and 95% Confidence Intervals for High Specific Gravity-Adjusted Phthalate Metabolite Levels and Selected Population Characteristics.

	High phthalate metabolite
Parameter	N	DBP metabolites	DEHP metabolites	MBzP	MCPP	MEP	MMP
Education
≤ Grade 12	9	1.0	1.0	1.0	1.0	1.0	1.0
Some college	16	0.6 (0.1, 3.2)	0.4 (0.1, 2.1)	0.2 (0.0, 1.1)	1.0 (0.2, 5.3)	0.4 (0.1, 2.1)	0.8 (0.1, 3.9)
College graduate	20	0.8 (0.2, 3.9)	0.4 (0.1, 2.1)	0.2 (0.0, 1.4)	0.5 (0.1, 2.6)	0.4 (0.1, 2.1)	1.9 (0.4, 9.2)
Income
≤ $45,000	11	1.0	1.0	1.0	1.0	1.0	1.0
$45,000 to < $90,000	16	0.9 (0.2, 3.9)	2.9 (0.6, 14.3)	1.2 (0.3, 5.6)	2.9 (0.6, 14.3)	0.3 (0.1, 1.3)	1.8 (0.4, 8.4)
≥$90,000	15	1.0 (0.2, 4.5)	1.5 (0.3, 7.5)	1.1 (0.2, 5.0)	0.9 (0.2, 4.5)	0.7 (0.1, 3.2)	3.5 (0.7, 17.9)
Not reported	3	*	*	*	*	*	*
Race
Caucasian	35	1.0	1.0	1.0	1.0	1.0	1.0
Nonwhite	10	6.0 (1.1, 32.5)	0.6 (0.2, 2.6)	0.4 (0.1, 1.6)	0.2 (0.0, 1.0)	3.1 (0.7, 14.1)	0.4 (0.1, 1.6)
Body Mass Index
Normal	11	1.0	1.0	1.0	1.0	1.0	1.0
Overweight	19	0.6 (0.2, 2.9)	0.9 (0.2, 3.9)	1.3 (0.3, 5.9)	2.4 (0.5, 11.1)	0.2 (0.0, 1.0)	0.5 (0.1, 2.4)
Obese	15	0.3 (0.1, 1.5)	1.8 (0.4, 8.7)	1.1 (0.2, 5.0)	1.5 (0.3, 7.5)	0.1 (0.0, 0.7)	0.4 (0.1, 1.9)
Current smoker
No	11	1.0	1.0	1.0	1.0	1.0	1.0
Yes	34	2.2 (0.5, 9.0)	0.9 (0.2, 3.3)	0.8 (0.2, 3.3)	0.9 (0.2, 3.3)	0.9 (0.2, 3.3)	2.2 (0.5, 9.0)
Alcohol servings
≤ 3/week	34	1.0	1.0	1.0	1.0	1.0	1.0
> 3/week	11	3.8 (0.9, 17.0)	0.5 (0.1, 2.1)	2.2 (0.5, 9.0)	0.3 (0.1, 1.3)	1.4 (0.3, 5.3)	0.8 (0.2, 3.3)

*Sample size not sufficient to compute odds ratios. Bolded denotes significant (p<0.05) association.

Crude and Adjusted Odds Ratios for Phthalate Metabolites and Low Semen Parameters.

	Sperm parameter
	Low sperm concentration		Low sperm motility		Low morphology
	Crude OR	Adjust. OR^a	Crude OR	Adjust. OR^b	Crude OR	Adjust. OR^c
Phthalate metabolite	(95% CI)	(95% CI)	(95% CI)	(95% CI)	(95% CI)	(95% CI)
DBP metabolites	2.5 (0.7, 9.2)	0.5 (0.1, 3.6)	1.1 (0.3, 3.6)	0.8 (0.2, 3.9)	1.6 (0.5, 5.6)	3.3 (0.7, 16.2)
DEHP metabolites	2.5 (0.7, 9.2)	5.4 (0.9, 30.8)	0.7 (0.2, 2.5)	1.6 (0.3, 7.1)	1.1 (0.3, 3.8)	0.9 (0.2, 3.2)
MBzP	1.6 (0.5, 5.8)	1.4 (0.3, 6.3)	0.7 (0.2, 2.5)	1.3 (0.3, 5.5)	1.6 (0.5, 5.6)	0.9 (0.2, 3.2)
MCPP	1.1 (0.3, 3.8)	1.3 (0.3, 5.5)	0.7 (0.2, 2.5)	0.4 (0.1, 1.6)	2.4 (0.7, 3.9)	7.6 (1.7, 33.3)
MEP	2.5 (0.7, 9.2)	6.5 (1.0, 43.6)	0.5 (0.1, 1.7)	0.8 (0.2, 3.3)	2.4 (0.7, 8.5)	3.4 (0.9, 13.8)
MMP	0.5 (0.1, 1.7)	0.8 (0.2, 3.8)	1.1 (0.3, 3.6)	3.2 (0.7, 14.2)	0.8 (0.2, 2.6)	0.9 (0.3, 3.3)

Crude odds ratios were adjusted for specific gravity at the individual subject level. Adjusted odds ratios were developed from multivariable logistic regression models in which specific gravity was adjusted at the group level as an independent variable in the model.

^aAdjusted for nonwhite race.

^bAdjusted for age and servings per week of alcohol.

^cAdjusted only for specific gravity as a separate covariate. Bolded denotes significant (p<0.05) association.

Association of Tertiles of Phthalate Metabolite Concentration with Semen Parameters.

	Sperm concentration^a			Sperm motility^b			Sperm morphology^c
Phthalate tertile	N^d	Crude OR (95% CI)	Adjusted OR (95% CI)	N	Crude OR (95% CI)	Adjusted OR (95% CI)	N	Crude OR (95% CI)	Adjusted OR (95% CI)
DEHP metabolites
1	3	1.0	1.0	4	1.0	1.0	7	1.0	1.0
2	4	1.6 (0.3–8.9)	1.97 (0.2–16.1)	6	0.8 (0.2–3.8)	0.7 (0.1–4.4)	11	1.2 (0.3–5.4)	1.8 (0.4–9.3)
3	7	3.1 (0.6–15.4)	6.65 (0.9–47.3)	6	0.7 (0.2–3.0)	0.7 (0.1–4.4)	10	1.1 (0.3–4.7)	1.2 (0.3, 5.6)
p for trend*		0.16	0.12		0.61	0.50		0.89	0.40
MCPP
1	5	1.0	1.0	5	1.0	1.0	9	1.0	1.0
2	3	0.4 (0.1–2.2)	0.1 (0.0–1.7)	7	1.4 (0.3–6.1)	1.2 (0.2–6.5)	7	0.4 (0.1–1.9)	0.5 (0.1–2.4)
3	6	1.2 (0.3–5.4)	1.5 (0.2–9.4)	4	0.7 (0.1–3.2)	0.4 (0.1–2.2)	12	2.2 (0.4–11.8)	3.1 (0.5–18.8)
p for trend*		0.78	0.78		0.60	0.60		0.37	0.4
MEP
1	2	1.0	1.0	6	1.0	1.0	7	1.0	1.0
2	5	2.7 (0.4–17.0)	3.6 (0.4–34.6)	6	0.80 (0.2–3.5)	0.7 (0.1–3.7)	10	1.67 (0.4–7.2)	4.24 (0.7–24.5)
3	7	5.3 (0.9–32.0)	6.5 (0.6–73.4)	4	0.49 (0.1–2.3)	0.5 (0.1–2.9)	11	2.75 (0.6–13.0)	7.04 (1.0–48.0)
p for trend*		0.06	0.05		0.37	0.45		0.20	0.14
MMP
1	4	1.0	1.0	3	1.0	1.0	10	1.0	1.0
2	6	1.1 (0.2–5.1)	1.3 (0.2–9.2)	6	1.5 (0.3–7.4)	2.3 (0.3–16.3)	9	0.49 (0.1–2.3)	0.71 (0.1–4.1)
3	4	0.7 (0.1–3.2)	0.7 (0.1–5.8)	7	2.1 (0.5–9.7)	3.7 (0.5–28.2)	9	0.47 (0.1–2.1)	0.62 (0.1–3.6)
p for trend*		0.78	0.80		0.33	0.21		0.34	0.40

^aAdjusted for nonwhite race and specific gravity as a separate covariate.

^bAdjusted for age, servings per week of alcohol (≥3 versus ≤3), and specific gravity as a separate covariate.

^cAdjusted only for specific gravity as a separate covariate.

^dIndicates the number of men with below the reference level (“low”) of the indicated sperm parameter and with the indicated phthalate exposure.

*p for trend reflects Mantel–Haenszel Chi-square distribution of tertiles among low semen parameters. Tertile cut points (μg/L): DEHP metabolites: 6.9–76.1, 76.2–157.9, 158.0–2, 126.5; MCPP:0.0–3.1, 3.2–7.1, 7.2–40.8; MEP: 14.8–68.5, 68.6–182.8, 182.7–2, 916.7; MMP: 0.0–1.8, 1.9–3.0, 3.1–60.4.