Copper Sex- and Cycle-Related Differences: Normal Range, Optimal Levels, and What Hormones Do to Your Results

Does sex change serum copper?

Yes. In a study of 55 men and 86 women aged 20 to 83 who were in apparent good health, plasma copper, immunoreactive ceruloplasmin and enzymatically measured ceruloplasmin were all significantly higher in women than in men, and higher in women taking oral contraceptives [1]. Erythrocyte superoxide dismutase and the ratio of enzymatic to immunoreactive ceruloplasmin were not significantly affected by age or sex in that study [1].

More than 95% of the copper in healthy plasma is carried on ceruloplasmin [5][6]. The authors of the study concluded that age, gender and hormone use need to be considered when these indicators are used to judge copper status [1].

What range does the number belong to?

Serum copper reference ranges vary by lab, so a result should be read against the range printed on the lab report. A general reference interval is not a separately established optimal target.

For the companion test, MedlinePlus gives an adult ceruloplasmin range of 20 to 40 mg/dL and notes that ranges vary slightly among labs [4].

The NIH Office of Dietary Supplements says copper status is not routinely assessed in practice and that no biomarker accurately and reliably measures copper status in the general population; studies rely on plasma or serum copper plus cuproenzyme activity such as ceruloplasmin oxidase and erythrocyte superoxide dismutase [6]. In one controlled trial, zinc lowered erythrocyte Cu,Zn-superoxide dismutase while plasma copper and ceruloplasmin activity stayed unchanged [7].

Do oral contraceptives raise copper?

Yes. In an 18-day controlled metabolic study, women using oral contraceptives had higher plasma copper than women who had never used them (P<0.01), while plasma zinc did not differ between the groups [2]. Copper balance did not differ either: mean retention was -0.13 mg/day in users and -0.16 mg/day in non-users on diets supplying about 2.0 mg of copper daily [2]. The blood level was higher without a matching difference in retention. MedlinePlus also lists birth control pill use among the causes of a higher ceruloplasmin [4].

Does the menstrual cycle matter?

MedlinePlus lists pregnancy and birth control pills as causes of a higher ceruloplasmin but gives no cycle-day guidance [4]. None of the other cited material addresses cycle phase.

What else pushes copper up or down

MedlinePlus lists acute and chronic infection, breast cancer or lymphoma, heart disease including heart attack, overactive thyroid, pregnancy, rheumatoid arthritis and birth control pill use as causes of a high ceruloplasmin [4]. Low ceruloplasmin is listed with chronic liver disease, intestinal malabsorption, malnutrition, Menkes syndrome, nephrotic syndrome and Wilson disease [4].

For a low result, the companion tests are serum copper, ceruloplasmin and 24-hour urine copper: in deficiency, serum copper and ceruloplasmin are low and urine copper is low, whereas in Wilson disease ceruloplasmin is low but urine copper is high [5][8].

Can zinc affect copper status?

Zinc can affect copper status through competition for intestinal absorption [5]. Copper enters intestinal cells through the Ctr1 transporter and leaves via ATP7A, and zinc competes at that level [5]. The NIH adult tolerable upper intake level for zinc is 40 mg/day, and chronic zinc intake of 150 to 450 mg/day is linked to low copper status [10].

In a 6-week controlled trial in healthy men, 25 mg of zinc twice daily lowered erythrocyte Cu,Zn-superoxide dismutase versus placebo (P<0.05 at 6 weeks), while plasma copper and ceruloplasmin ferroxidase activity were unchanged at 2, 4 or 6 weeks [7]. In that trial, blood copper looked normal while a functional marker fell. The severe cases in the literature involve large or prolonged zinc exposure, such as three men aged 21 to 47 with anemia, severe neutropenia and, in two, progressive neuropathy, diagnosed from bone marrow findings [11], and an adult who developed hypochromic-microcytic anemia, leukopenia and neutropenia after 10 months of excessive oral zinc and did not respond to iron [9].

A review of 55 published cases of copper deficiency myelopathy found women outnumbering men 3.6 to 1; risk factors were prior upper gastrointestinal surgery, zinc overload and malabsorption [8]. A case series of this kind cannot show how much more often women develop the condition.

What shifts how a result reads

• Whether oral contraceptives or other birth control pills were being used when the blood was drawn [1][4]
• Pregnancy status [4]
• Total daily zinc intake, compared with the 40 mg/day adult upper level [10]
• Any active infection or inflammatory condition [4]