Results of a recent ob­ser­va­tion­al study in­di­cate that a sub­stan­tial majority of recently diag­nosed mul­ti­ple myeloma patients have low testos­terone levels.

Researchers at Ohio State Uni­ver­sity tested testos­terone levels in the blood of over 550 people with a plasma cell disorder. More than 90 per­cent of the study par­tic­i­pants had either mul­ti­ple myeloma, smol­der­ing mul­ti­ple myeloma, MGUS, or a plasmacytoma. Across all the study par­tic­i­pants, 74 per­cent had testos­terone levels that were low given their gender and age.

Testosterone levels were measured within six months of diag­nosis. Among the study par­tic­i­pants who had active (symptomatic) mul­ti­ple myeloma, the measured testos­terone levels may have reflected the com­bined effect of their dis­ease and their myeloma treat­ment, as testos­terone levels were not always measured before the start of treat­ment.

The re­searchers found that study par­tic­i­pants were statistically more likely to have a low testos­terone level if they had a high body mass index (a measure of a person's weight that adjusts for their height) or if they had taken opiate pain relievers. There also was a trend for low albumin levels to be asso­ci­ated with low testos­terone levels.

The in­ves­ti­ga­tors did not find any statistically sig­nif­i­cant asso­ci­a­tion be­tween testos­terone levels and a patient's age, beta-2 microglobulin level, or creatinine level. Likewise, the presence or absence of high-risk chromosomal ab­nor­mal­i­ties did not have an effect on a patient's testos­terone levels, and men and women were equally likely to have testos­terone levels below the nor­mal range for their gender and age.

The re­searchers also explored whether there was any asso­ci­a­tion be­tween testos­terone levels and over­all sur­vival among the par­tic­i­pants in their study. Despite ap­proach­ing the issue from sev­er­al dif­fer­en­t perspectives, the re­searchers could not find any sig­nif­i­cant evi­dence of such an asso­ci­a­tion.

Testosterone, to­geth­er with estrogens, androgens, and vitamin D, play an im­por­tant role in bone build­ing. Given the importance of bone health in people with mul­ti­ple myeloma, the Ohio State re­searchers recog­nize that testos­terone replacement ther­apy might be con­sidered in cases where patients, par­tic­u­larly male patients, have especially low levels of the hormone.  The re­searchers neither rec­om­mend nor advise against replacement ther­apy. They do note, how­ever, that at least one recent study sug­gests that vitamin D supple­mentation may have a greater effect on bone growth than testos­terone replacement ther­apy.

Background In­for­ma­tion

Low testos­terone levels fre­quently oc­cur in older men, but age is not the only factor that can lead to low testos­terone levels.

The authors of the the Ohio State study note that mul­ti­ple myeloma and its treat­ments also may con­trib­ute to low testos­terone levels. For example, symp­toms of low testos­terone levels have been re­ported in mul­ti­ple myeloma patients who have re­ceived high-dose mel­phalan, and exposure to dexa­meth­a­sone also is asso­ci­ated with lowered testos­terone levels.

In their cur­rent study, the re­searchers sought to de­ter­mine whether there is a con­nec­tion be­tween testos­terone levels and a myeloma patient's personal and dis­ease char­ac­ter­istics. One hypothesis they explicitly wanted to test was whether a gain in chromosome 1q was asso­ci­ated with higher testos­terone levels.

Study Design

Data for the cur­rent study was drawn from the Ohio State Uni­ver­sity Multiple Myeloma and Amy­loid­osis Data Registry. To be in­cluded in the cur­rent study, registry par­tic­i­pants had to have a plasma cell disorder and have their blood (serum) testos­terone level tested within six months of diag­nosis. The study did not record whether par­tic­i­pants had started treat­ment for their dis­ease prior to their testos­terone testing.

Overall, the cur­rent study draws on data for 561 people (305 males and 121 females), 426 of whom had mul­ti­ple myeloma, 25 smol­der­ing myeloma, 55 MGUS (monoclonal gam­mop­athy of undetermined sig­nif­i­cance), 47 AL amy­loid­osis, and 8 a plasmacytoma.

Study Results

The re­searchers found that 74 per­cent of patients had low testos­terone levels for their gender and age. The mean testos­terone level for all patients in the study was 260 ng/dL. The levels were similar across all dis­eases in the male study par­tic­i­pants. It was 222.5 ng/dL in mul­ti­ple myeloma patients, 205.5 ng/dL in smol­der­ing myeloma patients, 212 ng/dL in MGUS patients, and 246 ng/dL in AL amy­loid­osis patients.

As they ex­pec­ted based on pre­vi­ous re­search, the re­searchers found that low testos­terone levels were asso­ci­ated with high body weight (as measured by a patient's body mass index) and with the use of opiate pain relievers. There also was a trend for low testos­terone levels to be asso­ci­ated with low albumin levels.

The re­searchers did not ob­serve, how­ever, any asso­ci­a­tion be­tween low testos­terone levels and age, beta-2 microglobulin levels, creatinine levels, and the absence or presence of high-risk chromosomal ab­nor­mal­i­ties (which were defined as t(4;14), t(14;16), and del(17p)).

Contrary to their ex­pec­ta­tions, the in­ves­ti­ga­tors found that patients with chromosome 1q trisomies and tetrasomies had the lowest median testos­terone levels. (A "trisomy" is chromosomal ab­nor­mal­ity where cells have three copies of a chromosome, instead of the usual two; a "tetrasomy" is when there are four copies of a chromosome.)

The re­searchers also used two dif­fer­en­t techniques to in­ves­ti­gate whether there was any con­nec­tion be­tween testos­terone levels and over­all sur­vival in the study par­tic­i­pants. The two technique were used separately for male and female study par­tic­i­pants, so a total of four dif­fer­en­t checks were done to see if there was an asso­ci­a­tion be­tween testos­terone levels and over­all sur­vival.

Only in one case – a comparison of sur­vival in male par­tic­i­pants with the highest and lowest testos­terone levels – was there an indi­ca­tion that over­all sur­vival might be lower in patients with lower testos­terone levels. The dif­fer­ence in sur­vival be­tween the two groups of males patients, how­ever, was not statistically sig­nif­i­cant.

When the re­searchers com­pared the data for the patients in their study to those of an on­go­ing national study in­ves­ti­gating the health and nutritional status of people in the United States, they found that the mean testos­terone level of the male patients in the national study were higher than those of the male patients in their study (389 ng/dL versus 260 ng/dL).

The re­­sults were similar when the authors com­pared the data for male patients in their study to those in a study of male hormone levels in elderly men from the general pop­u­la­tion. Once again, the patients in the Ohio State study had lower testos­terone levels than the men from the broader pop­u­la­tion (534 ng/dL versus 260 ng/dL).

(The re­searchers fre­quently focused the analyses in their study on the re­­sults for the men in their data set.)

For more in­­for­ma­tion, please see the study by John, S. et al., “Most mul­ti­ple myeloma patients have low testos­terone,” in Leukemia & Lymphoma, Octo­ber 2, 2018 (article preview).