1

Clinical Policy Title: Implantable testosterone pellets

Clinical Policy Number: 18.03.05

Effective Date: June 1, 2018

Initial Review Date: April 10, 2018

Most Recent Review Date: May 1, 2018

Next Review Date: May 2019

Related policies:

None.

ABOUT THIS POLICY: Prestige Health Choice has developed clinical policies to assist with making coverage determinations. Prestige Health Choice’s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peer-reviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of “medically necessary,” and the specific facts of the particular situation are considered by Prestige Health Choice when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. Prestige Health Choice’s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. Prestige Health Choice’s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, Prestige Health Choice will update its clinical policies as necessary. Prestige Health Choice’s clinical policies are not guarantees of payment.

Coverage policy

Prestige Health Choice considers the use of implantable hormone (testosterone) pellets to be clinically

proven and, therefore, medically necessary as replacement therapy for men who have low testosterone

levels due to disorders of the testicles, pituitary gland, or brain that cause hypogonadism, after courses

of intramuscular or topical forms of testosterone have provided an inadequate response, are

contraindicated, or the member is intolerant of these forms (FDA, 2015; CMS, 2015). Continuation of

treatment using pellets will be necessary only if the patient’s testosterone level fails to increase to the

normal range after six months of treatment (Bhasin, 2018).

In addition, Prestige Health Choice considers implantable testosterone pellets clinically proven and,

therefore, medically necessary, as part of gender reassignment therapy for female-to-male individuals if

courses of intramuscular or topical forms of testosterone have provided an inadequate response, are

contraindicated, or the patient is intolerant of these forms (WPATH, 2011).

Policy contains:

Androgen.

Hypogonadism.

Testopel®.

Testosterone.

2

Limitations:

Coverage determinations are subject to benefit limitations and exclusions as delineated by the state

Medicaid authority. The Florida Medicaid website may be accessed at

http://ahca.myflorida.com/Medicaid/.

Testosterone therapy in hormone pellet or other forms for reduced levels of testosterone (confirmed by

lab tests) due to aging is considered not clinically proven and, therefore, investigational/experimental

(FDA, 2015).

Testosterone therapy in hormone pellet or other forms for patients with breast or prostate cancer or

with a palpable prostate nodule or induration; with a prostate-specific antigen greater than 4 ng/mL or

greater than 3 ng/mL in men at high risk for prostate cancer; with untreated severe obstructive sleep

apnea; with severe lower urinary tract symptoms with International Prostate Symptom Score above 19;

or with uncontrolled or poorly controlled heart failure is considered not clinically proven and, therefore,

investigational/experimental (CMS, 2015; Bhasin, 2010).

Testosterone should not be prescribed as part of compounded hormones, such as in conjunction with

estrogen, as these compounds are not approved by the U.S. Food and Drug Administration (FDA) and

evidence for their effectiveness is lacking (ACOG, 2012; Santoro, 2016).

Alternative covered services:

None.

Background

Testosterone is a hormone generated by the testes essential for development and growth of male sex

organs and maintenance of secondary male characteristics such as facial hair (FDA, 2015). Testosterone

is present in women but at much lower levels than men. Levels of the hormone peak at about age 20

and starting in middle age decline by about 1 percent annually. The normal range of serum testosterone

is 270 to 1,100 (average 679) nanograms per deciliter of blood (Davis, 2016).

Hypogonadism is a disorder marked by low levels of testosterone diagnosed through blood tests. In

addition, the condition can occur from a variety of causes, including testicular problems, genetic

problems, chemotherapy damage, or pituitary gland/hypothalamus disorders (FDA, 2015). Symptoms of

hypogonadism can include reductions in libido, erections, physical energy, strength, stamina, and

mental aggressiveness, along with weight gain, aches and pains, and osteoporosis (Davis, 2016).

A study by the Endocrine Society used a sample of 1,475 American males ages 30–79 to estimate that

5.6 percent have symptomatic low testosterone (<300 ng/dL), a figure that rises to 18.4 percent for

males in their 70s. In addition, 24 percent and 11 percent had low total and free testosterone levels,

3

respectively, regardless of whether symptoms were present. The Society projects that by 2025, there

will be 6.5 million American males with symptomatic androgen deficiency, a rise of 38 percent from

2000 (Araujo, 2007).

The number of American males taking testosterone is rising rapidly. One study of 10,739,815 U.S. men

over age 40 documented that from 2001 to 2011, use of testosterone (androgen) more than tripled,

from 0.81 to 2.91 percent. Rates were greater for males in their 60s (3.75 percent, compared to 2.29

percent for males in their 40s), and in the South (3.77 percent in 2010, compared to the West [2.61

percent]), the Midwest (1.78 percent), and the Northeast (1.60 percent). A substantial proportion (25.28

percent) of users did not have their testosterone measured in the past 12 months. Common diagnoses

in the year prior to treatment initiation were hypogonadism (50.58 percent), fatigue (34.49 percent),

erectile dysfunction (31.88 percent), and psychosexual dysfunction (11.75 percent). Topical gel was the

most commonly used treatment mode, and also rose more than any type, i.e., fivefold from 2001 to

2011 (Baillargeon, 2013).

FDA-approved testosterone formulations include gels, solution, skin patch, intramuscular injection,

pellets implanted under the skin, and a buccal system applied to the upper gum or inner cheek. The FDA

endorses testosterone as replacement therapy only for men with hypogonadism due to disorders of the

testicles, pituitary gland, or brain. These conditions include failure of the testicles to produce

testosterone due to genetic problems, or damage from chemotherapy or infection. The FDA cautions

that the benefits and safety of administering testosterone to symptomatic males with low levels of the

hormone for no apparent reason other than aging have not been clinically proven (FDA, 2015).

The FDA also warns that possible increased risk of cardiovascular conditions, including heart attack,

stroke, and death, have been identified in some peer-reviewed studies, while others found no such risks.

The FDA encourages health providers to make patients aware of this potential risk when deciding to

start or continue testosterone treatment, and requires manufacturers to conduct trials addressing this

issue. Patients using testosterone should seek medical attention immediately if heart attack or stroke

symptoms (chest pain, shortness of breath or difficulty breathing, weakness in one part/side of the

body, or slurred speech) are present (FDA, 2015).

Testosterone pellets measure 3 mm x 9 mm and contain crystalline testosterone. Implantation is a brief

procedure performed in an office setting. After cleaning the skin of the upper hip or buttocks, an

anesthetic is injected and a small incision made. Typically, about 10–12 pellets are placed under the skin

near the hip with a trocar. Testosterone is gradually released over 3–6 months (Case-Lo, 2017).

Testopel® (Slate Pharmaceuticals) became the first FDA-approved implantable testosterone pellet

marketed in the United States in 2008. Pellets, as opposed to gels, eliminate the need for daily

applications, erratic absorption, low long-term compliance rates, risk of transferring the gel to family

members, and expense of the monthly prescriptions. Each pellet contains 75 mg of testosterone

(McCullough, 2014).

4

The FDA guideline endorses implantable pellets of testosterone as replacement therapy for men who

have hypogonadism from disorders of the testicles, pituitary gland, or brain. Pellets should only be used

after courses of intramuscular and topical forms of testosterone have failed (FDA, 2015).

Other testosterone-related guidelines do not specifically address pellets. The Endocrine Society

guideline recommends testosterone therapy for men with symptomatic androgen deficiency to induce

and maintain secondary sex characteristics and to improve their sexual function, sense of well-being,

muscle mass and strength, and bone mineral density (Bhasin, 2010). A March 2018 update of the

Endocrine Society guideline addresses diagnostic techniques, criteria indicating treatment is needed,

and monitoring. It also states the goal for success with any testosterone therapy is to achieve

testosterone concentrations in the mid-normal range during treatments (Bhasin, 2018). This goal is

based on results of the Testosterone Trial sponsored by the National Institutes of Health, in which 91

percent of 709 males over age 65 given testosterone increased and remained in the mid-normal range

3–12 months after treatment began (Snyder, 2016).

The Canadian Men’s Health Foundation Multidisciplinary Guidelines Task Force on Testosterone

Deficiency recommends the same criteria as the FDA for treating males with low testosterone, without

specifying pellets (Morales, 2015).

Searches

Prestige Health Choice searched PubMed and the databases of:

UK National Health Services Centre for Reviews and Dissemination.

Agency for Healthcare Research and Quality’s National Guideline Clearinghouse and other

evidence-based practice centers.

The Centers for Medicare & Medicaid Services (CMS).

We conducted searches on February 16, 2018. Search terms were: “testosterone,” “pellets,”

“hypogonadism,” and “implant.”

We included:

Systematic reviews, which pool results from multiple studies to achieve larger sample sizes

and greater precision of effect estimation than in smaller primary studies. Systematic

reviews use predetermined transparent methods to minimize bias, effectively treating the

review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies.

Guidelines based on systematic reviews.

Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple

cost studies), reporting both costs and outcomes — sometimes referred to as efficiency

studies — which also rank near the top of evidence hierarchies.

Findings

5

Health status in males taking testosterone have been tracked in numerous reports. A study of 1,167

Danish males ages 30–60 was followed a median of 15.2 years after testosterone levels were recorded.

During follow-up, 36.1 percent (n=421) died. Men with the largest (below 10th percentile) in total

testosterone had a significantly higher mortality risk (hazard ratio 1.60) than all others (Holmboe, 2018).

Some concern has been raised about testosterone therapy increasing the risk of cardiovascular

morbidity. However, a recent literature review contends that only a few studies raised these concerns,

and these were marred by serious methodological and analytical flaws; the article called the concerns

“unsubstantiated” and that numerous trials and meta-analyses showed no such risk (Traish, 2016).

A systematic review of 75 studies (n=5,464) supported the conclusion of no causal association between

testosterone therapy and cardiovascular disease (Corona, 2014). Another review (n=509) tracked males

(average age 54 years) taking or not taking testosterone for 10 years, probably the first long-term study

of testosterone risk. The review found an insignificant difference (4.4 percent versus 3.2 percent) in all-

cause mortality between the two groups, and concluded that long-term therapy was safe (Eisenberg,

2015).

A systematic review of 45 trials (n=5,328) followed men with hypogonadism using testosterone for an

average of 10.6 months. Testosterone supplementation was not linked with increased cardiovascular

disease risk (p = 0.45). The rate of cardiovascular events was not significantly elevated for intramuscular

testosterone (p = 0.91) or oral testosterone (p = 0.22), but was significantly greater for transdermal

testosterone (p = 0.004) (Albert, 2016). A meta-analysis of 30 randomized trials showed no significant

increase in risk of myocardial infarction, stroke, or mortality from testosterone use (Alexander, 2017).

A large systematic review and meta-analysis (87 randomized controlled trials and 51 nonrandomized

studies) included studies of males over age 18 with low free and/or total testosterone tracked for at

least three months. Significant increases in testosterone levels, along significant improvement in quality

of life, libido, depression, and erectile dysfunction were identified (Elliott, 2017).

One early review of 380 men with hypogonadism undergoing 702 insertions of Testopel found that 6–10

or more pellets (450–750 or more mg) boosted total testosterone levels into normal range (over 300

nanograms per deciliter) after one month, and sustained normal levels for 4–6 months. Optimal and

well tolerated results were eventually noted to be eight or more pellets (McCullough, 2012). Another

dosing study from the same year concluded 10 – 12 pellets yielded optimal results (Pastuszak, 2012).

An early safety study of the safety of Testopel pellets included 80 men with 292 implant procedures.

Compared to historical data of the Organon testosterone pellet, Testopel had a lower infection rate (0.3

percent versus 1.4–6.8 percent), and a lower pellet extrusion rate (0.3 percent versus 8.5–12.0 percent).

No infections or pellet extrusions were reported and patient satisfaction was high (Cavender, 2009).

Outcomes comparing implantable testosterone pellets with injections, oral administration, and topical

(gels) have been conducted. A systematic review of 59 studies (n=5,078), documented that, compared

6

to placebo, parenteral and transdermal approaches were significantly more effective at increasing

testosterone (mean differences 7.69 and 7.57) than were oral preparations (2.39) (Corona, 2016).

A systematic review of 16 randomized controlled trials (n=1,921) included those where subjects were

followed for six months (seven trials) or 12 months (nine trials). Overall, testosterone lowered Aging

Male Symptoms (p=0.0002), including higher lean body mass (p=0.007), lower fat mass (p=0.06,

borderline significant), and lower total cholesterol (p=0.01). Nonsignificant changes included body

weight, body mass index, bone mineral density, and prostate-specific antigen. Average reductions in

Aging Male Symptoms with transdermal methods (short-term) was significant at p=0.0001, but not

significant for injections at p=0.69.

The study also documented insignificant differences between transdermal, oral, and injection modes of

therapy for body weight (p=0.23, 0.38, 0.55), body mass index (p=0.86, 0.85, 0.91), and bone mineral

density (p=0.26, 0.60, 0.17). Patients in the transdermal group had significantly higher prostate-specific

antigen (p=0.0002 versus 0.81 and 0.27) and had significantly higher rates of adverse events (Guo,

2016).

In a systematic review of 15 studies (n=739), average prostate-specific antigen was compared by type of

testosterone treatment. In four studies, the difference in mean prostate-specific antigen levels were

similar between patients who received transdermal testosterone and controls (p<0.116), but

significantly worse for those given intramuscular testosterone (p<0.001). In two studies, the difference

in change in levels were similar for both transdermal and intramuscular approaches (p<0.875, p<0.787)

(Kang, 2015).

A systematic review of 22 randomized controlled trials (n=2,351), split into 11 short-term (<12 months)

and 11 long-term (12–36 months) studies, compared prostate-related outcomes for testosterone

therapy with placebo. Odds ratios for transdermal, oral, or injection administration of testosterone

short-term were insignificantly low for prostate cancer (1.10, 0.0, and 0.39) and prostate nodules (1.01,

0.0, and 0.0). Long-term odds ratios were generally higher, with no difference from placebo (3.06, 0.19,

and 2.09 for prostate cancer, and 1.00, 0.97, and 3.13 for prostate nodules) (Cui, 2015).

A study compared men with hypogonadism treated with gels (n=47), injections (n=57), or pellets (n=74),

followed for three years. Increases in total and free testosterone were observed for all groups, as they

were for estradiol. The injection group had the highest increase, due to the much sharper rise in the first

three months after therapy was initiated. Hemoglobin and hematocrit were higher in the injection group

than in gel or pellet groups. No significant increases in prostate-specific antigen levels were observed.

Erythrocytosis (hematocrit over 50 percent) was more common with injections (66.7 percent) than with

gels (12.8 percent) or pellets (35.1 percent, p < 0.0001) (Pastuszak, 2015).

Patient satisfaction among 382 patients using testosterone were similar across type of treatment (gels

68 percent, injections 73 percent, and implantable pellets 70 percent (Kovac, 2014).

7

Policy updates:

None.

Summary of clinical evidence:

Citation Content, Methods, Recommendations

Albert (2016)

Risk of cardiovascular

disease from testosterone

Key points:

Systematic review of 45 trials (n=5,328), men with hypogonadism on testosterone.

Subjects followed for an average of 10.6 months.

Testosterone supplementation not linked to cardiovascular disease risk (p = 0.45).

Cardiovascular event rate not significantly elevated for intramuscular (p = 0.91) or oral

(p = 0.22), but significantly greater for transdermal testosterone (p=0.0004).

Corona (2016)

Effectiveness of various

types of testosterone in

raising testosterone levels

Key points:

Systematic review of 59 studies (n=5,078), comparing types of testosterone therapy

ability to increase testosterone levels.

Compared to placebo, parenteral and transdermal approaches were significantly more

effective (mean differences 7.69 and 7.57) than oral preparations (2.39).

Guo (2016)

Changes in aging male

symptoms from testosterone

Key points:

Systematic review of 16 randomized controlled trials (n=1,921); subjects followed for 12

months.

All testosterone lowered Aging Male Symptoms (p=0.0002).

Significant decreases in higher lean body mass (p=0.007), lower fat mass (p=0.06,

borderline significant), and lower total cholesterol (p=0.01).

Nonsignificant changes included body weight, body mass index, bone mineral density,

and prostate-specific antigen.

Average reductions in Aging Male Symptoms with transdermal methods (short-term)

was significant at p=0.0001, but not significant for injections (long-term) at p=0.69.

Insignificant differences between transdermal, oral, and injection modes of therapy for

body weight (p=0.23, 0.38, 0.55), body mass index (p=0.86, 0.85, 0.91), and bone

mineral density (p=0.26, 0.60, 0.17).

Transdermal administration had significantly higher increased prostate- specific antigen

(p=0.0002 versus 0.81 and 0.27) and had significantly higher rates of adverse events.

Cui (2015)

Risk of prostate disease

from testosterone

Key points:

Systematic review of 22 randomized controlled trials (n=2,351) included 11 short-term

(<12 months) and 11 long-term (12–36 months) studies.

Prostate-related outcomes for types of testosterone therapy compared with placebo.

Odds ratios for transdermal, oral, or injection administration of testosterone short-term

were insignificantly low for prostate cancer (1.10, 0.0, and 0.39).

8

Citation Content, Methods, Recommendations

Odds ratios for transdermal, oral, or injection administration of testosterone short-term

were insignificantly lower for prostate nodules (1.01, 0.0, and 0.0).

Odds ratios long-term for prostate cancer were 3.06, 0.19, and 2.09.

Odds ratios long-term for prostate nodules were 1.00, 0.97, and 3.13.

Pastuszak (2015)

Changes in levels of other

hormones in males taking

testosterone

Key points:

Study of changes in serum hormones, erythrocytosis, lipids, and prostate- specific

antigen for men with hypogonadism treated with gels (n=47), injections (n=57), or

pellets (n=74).

Subjects were followed for three years.

Rises in total and free testosterone and in estradiol were observed for all groups.

The injection group had the highest increase due to the much sharper rise in the first

three months after therapy was initiated.

Hemoglobin and hematocrit were higher for injections than gel or pellet groups.

No significant increases in prostate- specific antigen levels were observed.

Erythrocytosis (hematocrit over 50%) more common with injections (66.7%) than gels

(12.8%) or pellets (35.1%, p<0.0001).

References

Professional society guidelines/other:

American College of Obstetricians and Gynecologists (ACOG). Committee on Gynecologic Practice and

the American Society for Reproductive Medicine Practice Committee. Number 532, August 2012.

https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-

Gynecologic-Practice/Compounded-Bioidentical-Menopausal-Hormone-Therapy. Accessed February 15,

2018.

Bhasin S, Cunningham GR, Hayes FJ, et al. Task Force, Endocrine Society. Testosterone therapy in men

with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol

Metab. 2010;95(6):2536 – 39.

Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: An

Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018. Doi: 10.1210/jc.2018-00229.

Case-Lo C. Skin Deep: Testosterone Pellets 101. Healthline Inc., September 29, 2017.

https://www.healthline.com/health/testosterone-pellets. Accessed February 16, 2018.

Davis CP. High and low testosterone levels in men. MedicineNet, June 28, 2016.

https://www.medicinenet.com/high_and_low_testosterone_levels_in_men/views.htm. Accessed

February 16, 2018.

9

Morales A, Bebb RA, Manjoo P, et al. Canadian Men’s Health Foundation Multidisciplinary Guidelines

Task Force on Testosterone Deficiency. Diagnosis and management of testosterone deficiency syndrome

in men: clinical practice guideline. CMAJ. 2015;187(18):1369 – 77.

Santoro N, Braunstein GD, Butts CL, et al. Compounded bioidentical hormones in endocrinology

practice: An Endocrine Society scientific statement. J Clin Endocrinol Metab. 2016;101(4):1348 – 43.

U.S. Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA cautions about using

testosterone products for low testosterone due to aging; requires labeling change to inform of possible

increased risk of heart attack and stroke with use. March 3, 2015.

https://www.fda.gov/Drugs/DrugSafety/ucm436259.htm. Accessed February 16, 2018.

World Professional Association for Transgender Health, Inc. (WPATH). Standard of Care (SOC) Version 7.

Minneapolis MN: WPATH, September 14, 2011.

http://www.wpath.org/site_page.cfm?pk_association_webpage_menu=1351&pk_association_webpage

=3926. Accessed April 27, 2018.

Peer-reviewed references:

Albert SG, Morley JE. Testosterone therapy, association with age, initiation and mode of therapy with

cardiovascular events: a systematic review. Clin Endocrinol (Oxf). 2016;85(3):436 – 43.

Alexander GC, Iyer G, Lucas E, Lin D, Singh S. Cardiovascular risks of exogenous testosterone use among

men: A systematic review and meta-analysis. Am J Med. 2017;130(3):293 – 305.

Araujo AB, Esche GR, Kupelian V, et al. Prevalence of symptomatic androgen deficiency in men. J Clin

Endocrinol Metab. 2007;92(11):4241 – 47.

Baillargeon J, Urban RJ, Ottenbacher KJ, Pierson KS, Goodwin JS. Trends in Androgen Prescribing in the

United States, 2001 to 2011. JAMA Intern Med. 2013;173(15):1465 – 66.

Cavender RK, Fairall M. Subcutaneous testosterone pellet implant (Testopel) therapy for men with

testosterone deficiency syndrome: a single-site retrospective safety analysis. J Sex Med. 2009;6(11):3177

– 92.

Corona G, Giagulli VA, Maseroli E, et al. Therapy of endocrine disease: Testosterone supplementation

and body composition: results from a meta-analysis study. Eur J Endocrinol. 2016;174(3):R99 – 116.

Corona G, Maseroli E, Rastrelli G, et al. Cardiovascular risk associated with testosterone-boosting

medications: a systematic review and meta-analysis. Expert Opin Drug Saf. 2014;13(10):1327 – 51.

Cui Y, Zong H, Yan H, Zhang Y. The effect of testosterone replacement therapy on prostate cancer: a

systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2014;17(2):132 – 43.

10

Eisenberg ML, Li S, Herder D, Lamb DJ, Lipshultz LI. Testosterone therapy and mortality risk. Int J Impot

Res. 2015;27(2):46 – 48.

Elliott J, Kelly SE, Millar AC, et al. Testosterone therapy in hypogonadal men: a systematic review and

network meta-analysis. BMJ Open. 2017;7(11):e015284.

Guo C, Gu W, Liu M, et al. Efficacy and safety of testosterone replacement therapy in men with

hypogonadism: A meta-analysis study of placebo-controlled trials. Exp Ther Med. 2016;11(3):853 – 63.

Holmboe SA, Skakkebaek NE, Juul A, et al. Individual testosterone decline and future mortality risk in

men. Eur J Endocrinol. 2018;178(1):123 – 30.

Kang DY, Li HJ. The effect of testosterone replacement therapy on prostate-specific antigen (PSA) levels

in men being treated for hypogonadism: a systematic review and meta-analysis. Medicine (Baltimore).

2015;94(3):e410. Doi: 10.1097/MD.0000000000000410.

Kovac JR, Rajanahally S, Smith RP, Coward RM, Lamb DJ, Lipshultz LI. Patient satisfaction with

testosterone replacement therapies: the reasons behind the choices. J Sex Med. 2014;11(2):553 – 62.

McCullough A. A review of testosterone pellets in the treatment of hypogonadism. Curr Sex Health Rep.

2014;6(4):265 – 69.

McCullough AR, Khera M, Goldstein I, Hellstrom WJ, Morgentaler A, Levine LA. A multi-institutional

observational study of testosterone levels after testosterone pellet (Testopel(®)) insertion. J Sex Med.

2012;9(2):594 – 601.

Pastuszak AW, Gomez LP, Scovell JM, Khera M, Lamb DJ, Lipshultz LI. Comparison of the effects of

testosterone gels, injections, and pellets on serum hormones, erythrocytosis, lipids, and prostate-

specific antigen. Sex Med. 2015;3(3):165 – 73.

Pastuszak AW, Mittakanti H, Liu JS, Gomez L, Lipshultz LI, Khera M. Pharmacokinetic evaluation and

dosing of subcutaneous testosterone pellets. J Androl. 2012;33(5):927 – 37.

Snyder PJ, Bhasin S, Cunningham GR, et al. Testosterone Trials Investigators. Effects of testosterone

treatment in older men. N Eng J Med. 2016;374(7):611 – 24.

Traish AM. Testosterone therapy in men with testosterone deficiency: are the benefits and

cardiovascular risks real or imagined? Am J Physiol Regul Integr Comp Physiol. 2016;311(3):R566 – 73.

CMS National Coverage Determinations (NCDs):

No NCDs identified as of the writing of this policy.

Local Coverage Determinations (LCDs):

11

L33412. Testosterone pellets (Testopel®). Effective date October 1, 2015.

https://www.cms.gov/medicare-coverage-database/details/lcd-

details.aspx?LCDId=33412&ver=5&CoverageSelection=Both&ArticleType=All&PolicyType=Final&s=All&K

eyWord=testosterone&KeyWordLookUp=Title&KeyWordSearchType=And&bc=gAAAACAAAAAA&.

Accessed February 19, 2018.

L36538. Treatment of males with low testosterone. Effective date July 12, 2016.

https://www.cms.gov/medicare-coverage-database/details/lcd-

details.aspx?LCDId=36538&ver=10&CoverageSelection=Both&ArticleType=All&PolicyType=Final&s=All&

KeyWord=testosterone&KeyWordLookUp=Title&KeyWordSearchType=And&bc=gAAAACAAAAAA&.

Accessed February 19, 2018.

L36569. Treatment of males with low testosterone. Effective date July 12, 2016.

https://www.cms.gov/medicare-coverage-database/details/lcd-

details.aspx?LCDId=36569&ver=11&CoverageSelection=Both&ArticleType=All&PolicyType=Final&s=All&

KeyWord=testosterone&KeyWordLookUp=Title&KeyWordSearchType=And&bc=gAAAACAAAAAA&.

Accessed February 19, 2018.

Commonly submitted codes

Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is

not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and

bill accordingly.

CPT Code Description Comments

11980 Subcutaneous hormone pellet implantation (implantation of estradiol and/or

testosterone pellets beneath the skin)

ICD-10 Code Description Comments

D35.2 Benign neoplasm of pituitary gland

D44.3 Neoplasm of uncertain behavior of pituitary gland

E23.0 Hypopituitarism

E23.1 Drug-induced hypopituitarism

E23.3 Hypothalamic dysfunction, not elsewhere classified

E23.6 Other disorders of pituitary gland

E23.7 Disorder of pituitary gland, unspecified

E29.1 Testicular hypofunction

E29.8 Other testicular dysfunction

E30.0 Delayed puberty

E89.5 Postprocedural testicular hypofunction

N50.89 Other specified disorders of the male genital organs

12

HCPCS

Level II Code Description Comments

S0189 Testosterone pellet, 75 mg