Statement of Principles

concerning

HYPOGONADISM
(Balance of Probabilities)

(No. 74 of 2021)

The Repatriation Medical Authority determines the following Statement of Principles under subsection 196B(3) of the Veterans' Entitlements Act 1986.

Dated                                           21 May 2021

Contents

1 Name

2 Commencement

3 Authority

4 Application

5 Definitions

6 Kind of injury, disease or death to which this Statement of Principles relates

7 Basis for determining the factors

8 Factors that must exist

9 Relationship to service

10 Factors referring to an injury or disease covered by another Statement of Principles

Schedule 1 - Dictionary

1 Definitions

1               Name

This is the Statement of Principles concerning hypogonadism (Balance of Probabilities) (No. 74 of 2021).

2               Commencement

              This instrument commences on 21 June 2021.

3               Authority

This instrument is made under subsection 196B(3) of the Veterans' Entitlements Act 1986.

4               Application

This instrument applies to a claim to which section 120B of the VEA or section 339 of the Military Rehabilitation and Compensation Act 2004 applies.

5               Definitions

The terms defined in the Schedule 1 - Dictionary have the meaning given when used in this instrument.

6               Kind of injury, disease or death to which this Statement of Principles relates

(1)          This Statement of Principles is about hypogonadism and death from hypogonadism.

Meaning of hypogonadism

(2)          For the purposes of this Statement of Principles, hypogonadism:

(a)          means deficient production of testosterone from the testis or estrogen from the ovary, or deficient production of ova (eggs) or sperm, where any such deficiency is associated with clinical symptoms and signs or a requirement for treatment; and

(b)          includes:

(i)            primary hypogonadism;

(ii)         secondary hypogonadism (also known as central hypogonadism and hypogonadotropic hypogonadism); and

(iii)       infertility due to endocrine or gonadal pathology; and

(c)          excludes heritable and congenital forms of hypogonadism, compensated hypogonadism, diminished ovarian reserve, naturally occurring menopause and abnormal semen analysis.

Note 1: Associated clinical symptoms and signs of hypogonadism may include loss of secondary sexual characteristics, loss of sexual function and loss of reproductive function (endocrine or gonadal infertility).

Note 2: infertility is defined in the Schedule 1 - Dictionary.

Death from hypogonadism

(3)          For the purposes of this Statement of Principles, hypogonadism, in relation to a person, includes death from a terminal event or condition that was contributed to by the person's hypogonadism.

Note: terminal event is defined in the Schedule 1 - Dictionary.

7               Basis for determining the factors

On the sound medical‑scientific evidence available, the Repatriation Medical Authority is of the view that it is more probable than not that hypogonadism and death from hypogonadism can be related to relevant service rendered by veterans or members of the Forces under the VEA, or members under the MRCA.

Note: MRCA, relevant service and VEA are defined in the Schedule 1 - Dictionary.

8               Factors that must exist

At least one of the following factors must exist before it can be said that, on the balance of probabilities, hypogonadism or death from hypogonadism is connected with the circumstances of a person's relevant service:

(1)          having hypopituitarism involving deficiency of follicle stimulating hormone or luteinising hormone at the time of the clinical onset of hypogonadism;

(2)          having hyperprolactinaemia at the time of the clinical onset of hypogonadism;

(3)          for males only, having a spinal cord injury resulting in paraplegia or tetraplegia before the clinical onset of hypogonadism;

(4)          having blunt or penetrating trauma to:

(a)          both ovaries or testes; or

(b)          a single functional ovary or testis, where there is only one functional ovary or testis;

sufficient to cause gonadal atrophy before the clinical onset of hypogonadism;

(5)          having surgical excision of:

(a)          both ovaries or testes; or

(b)          a single functional ovary or testis, where there is only one functional ovary or testis;

before the clinical onset of hypogonadism;

(6)          undergoing a course of therapeutic radiation for cancer, where:

(a)          both ovaries or testes; or

(b)          a single functional ovary or testis, where there is only one functional ovary or testis;

were in the field of radiation before the clinical onset of hypogonadism;

(7)          having infection with human immunodeficiency virus before the clinical onset of hypogonadism;

(8)          for males only, having infection with Mycobacterium leprae before the clinical onset of hypogonadism;

Note: Mycobacterium leprae is the organism that causes leprosy.

(9)          having infection with Trypanosoma brucei before the clinical onset of hypogonadism;

Note: Trypanosoma brucei is the organism that causes African sleeping sickness (trypanosomiasis).

(10)      having mumps orchitis as an adult affecting:

(a)          both testes; or

(b)          a single functional testis, where there is only one functional testis;

before the clinical onset of hypogonadism;

(11)      having an infiltrative disease from the specified list of infiltrative diseases of:

(a)          both ovaries or testes; or

(b)          a single functional ovary or testis, where there is only one functional ovary or testis;

before the clinical onset of hypogonadism;

Note: specified list of infiltrative diseases is defined in the Schedule 1 - Dictionary.

(12)      for males only, having a testicular varicocoele before the clinical onset of hypogonadism;

(13)      having infarction of:

(a)          both ovaries or testes; or

(b)          a single functional ovary or testis, where there is only one functional ovary or testis;

within the 1 year before the clinical onset of hypogonadism;

(14)      having sickle-cell disorder before the clinical onset of hypogonadism;

(15)      having a bone marrow or stem cell transplant before the clinical onset of hypogonadism;

(16)      having cirrhosis of the liver at time of the clinical onset of hypogonadism;

(17)      having chronic kidney disease at time of the clinical onset of hypogonadism;

Note: chronic kidney disease is defined in the Schedule 1 - Dictionary.

(18)      having anorexia nervosa at the time of the clinical onset of hypogonadism;

(19)      taking a course of systemic cytotoxic drugs for treatment of a malignant neoplasm before the clinical onset of hypogonadism;

(20)      taking gonadotrophin releasing hormone agonists or antagonists as androgen or estrogen deprivation therapy for at least 1 year within the 2 years before the clinical onset of hypogonadism;

(21)      having active epilepsy before the clinical onset of hypogonadism;

Note: active epilepsy is defined in the Schedule 1 - Dictionary.

(22)      taking a drug from the Specified List 1 of drugs before the clinical onset of hypogonadism;

Note: Specified List 1 of drugs is defined in the Schedule 1 - Dictionary.

(23)      taking an immune checkpoint inhibitor within the 1 year before the clinical onset of hypogonadism;

Note: immune checkpoint inhibitor is defined in the Schedule 1 - Dictionary.

(24)      taking a drug from the Specified List 2 of drugs, which cannot be ceased or substituted, at the time of the clinical onset of hypogonadism;

Note: Specified List 2 of drugs is defined in the Schedule 1 - Dictionary.

(25)      taking a drug which cannot be ceased or substituted and which is associated in the individual with the clinical onset of hypogonadism during drug therapy and either:

(a)          the improvement of hypogonadism within 2 months of discontinuing or tapering drug therapy; or

(b)           the redevelopment of hypogonadism on rechallenge with the same drug; and

where taking the drug continued for at least the 30 days before the clinical onset of hypogonadism;

(26)      inhaling fumes from a metal from the specified list of metals or a compound containing a metal from the specified list of metals:

(a)          for a cumulative period of at least 2,000 hours before the clinical onset of hypogonadism; and

(b)          if that exposure has ceased before the clinical onset of hypogonadism, then that onset occurred within 2 years of cessation;

Note: fumes and specified list of metals are defined in the Schedule 1 - Dictionary.

(27)      inhaling, ingesting or having cutaneous contact with a chemical agent from the specified list of chemical agents:

(a)          for a cumulative period of at least 2,000 hours before the clinical onset of hypogonadism; and

(b)          if that exposure has ceased before the clinical onset of hypogonadism, then that onset occurred within 2 years of cessation;

Note: specified list of chemical agents is defined in the Schedule 1 - Dictionary.

(28)      for females only, having smoked tobacco products:

(a)          in an amount of at least 5 pack-years before the clinical onset of hypogonadism; and

(b)          if smoking has ceased before the clinical onset of hypogonadism, then that onset occurred within 10 years of cessation;

Note: one pack-year is defined in the Schedule 1 - Dictionary.

(29)      for males only, having alcohol use disorder before the clinical onset of hypogonadism;

(30)      for females only, being underweight for at least the 5 years before the clinical onset of hypogonadism;

Note: being underweight is defined in the Schedule 1 - Dictionary.

(31)      having hypopituitarism involving deficiency of follicle stimulating hormone or luteinising hormone at the time of the clinical worsening of hypogonadism;

(32)      having hyperprolactinaemia at the time of the clinical worsening of hypogonadism;

(33)      for males only, having a spinal cord injury resulting in paraplegia or tetraplegia before the clinical worsening of hypogonadism;

(34)      having blunt or penetrating trauma to:

(a)          both ovaries or testes; or

(b)          a single functional ovary or testis, where there is only one functional ovary or testis;

sufficient to cause gonadal atrophy before the clinical worsening of hypogonadism;

(35)      having surgical excision of:

(a)          both ovaries or testes; or

(b)          a single functional ovary or testis, where there is only one functional ovary or testis;

before the clinical worsening of hypogonadism;

(36)      undergoing a course of therapeutic radiation for cancer, where:

(a)          both ovaries or testes; or

(b)          a single functional ovary or testis, where there is only one functional ovary or testis;

were in the field of radiation before the clinical worsening of hypogonadism;

(37)      having infection with human immunodeficiency virus before the clinical worsening of hypogonadism;

(38)      for males only, having infection with Mycobacterium leprae before the clinical worsening of hypogonadism;

Note: Mycobacterium leprae is the organism that causes leprosy.

(39)      having infection with Trypanosoma brucei before the clinical worsening of hypogonadism;

Note: Trypanosoma brucei is the organism that causes African sleeping sickness (trypanosomiasis).

(40)      having mumps orchitis as an adult affecting:

(a)          both testes; or

(b)          a single functional testis, where there is only one functional testis;

before the clinical worsening of hypogonadism;

(41)      having an infiltrative disease from the specified list of infiltrative diseases of:

(a)          both ovaries or testes; or

(b)          a single functional ovary or testis, where there is only one functional ovary or testis;

before the clinical worsening of hypogonadism;

Note: specified list of infiltrative diseases is defined in the Schedule 1 - Dictionary.

(42)      for males only, having a testicular varicocoele before the clinical worsening of hypogonadism;

(43)      having infarction of:

(a)          both ovaries or testes; or

(b)          a single functional ovary or testis, where there is only one functional ovary or testis;

within the 1 year before the clinical worsening of hypogonadism;

(44)      having sickle-cell disorder before the clinical worsening of hypogonadism;

(45)      having a bone marrow or stem cell transplant before the clinical worsening of hypogonadism;

(46)      having cirrhosis of the liver at time of the clinical worsening of hypogonadism;

(47)      having chronic kidney disease at time of the clinical worsening of hypogonadism;

Note: chronic kidney disease is defined in the Schedule 1 - Dictionary.

(48)      having anorexia nervosa at the time of the clinical worsening of hypogonadism;

(49)      taking a course of systemic cytotoxic drugs for treatment of a malignant neoplasm before the clinical worsening of hypogonadism;

(50)      taking gonadotrophin releasing hormone agonists or antagonists as androgen or estrogen deprivation therapy for at least 1 year within the 2 years before the clinical worsening of hypogonadism;

(51)      having active epilepsy before the clinical worsening of hypogonadism;

Note: active epilepsy is defined in the Schedule 1 - Dictionary.

(52)      taking a drug from the Specified List 1 of drugs before the clinical worsening of hypogonadism;

Note: Specified List 1 of drugs is defined in the Schedule 1 - Dictionary.

(53)      taking an immune checkpoint inhibitor within the 1 year before the clinical worsening of hypogonadism;

Note: immune checkpoint inhibitor is defined in the Schedule 1 - Dictionary.

(54)       taking a drug from the Specified List 2 of drugs, which cannot be ceased or substituted, at the time of the clinical worsening of hypogonadism;

Note: Specified List 2 of drugs is defined in the Schedule 1 - Dictionary.

(55)      taking a drug which cannot be ceased or substituted and which is associated in the individual with the clinical worsening of hypogonadism during drug therapy and either:

(a)          the improvement of hypogonadism within 2 months of discontinuing or tapering drug therapy; or

(b)           the clinical worsening of hypogonadism on rechallenge with the same drug; and

where taking the drug continued for at least the 30 days before the clinical worsening of hypogonadism;

(56)      inhaling fumes from a metal from the specified list of metals or a compound containing a metal from the specified list of metals:

(a)          for a cumulative period of at least 2,000 hours before the clinical worsening of hypogonadism; and

(b)          if that exposure has ceased before the clinical worsening of hypogonadism, then that worsening occurred within 2 years of cessation;

Note: fumes and specified list of metals are defined in the Schedule 1 - Dictionary.

(57)      inhaling, ingesting or having cutaneous contact with a chemical agent from the specified list of chemical agents:

(a)          for a cumulative period of at least 2,000 hours before the clinical worsening of hypogonadism; and

(b)          if that exposure has ceased before the clinical worsening of hypogonadism, then that worsening occurred within 2 years of cessation;

Note: specified list of chemical agents is defined in the Schedule 1 - Dictionary.

(58)      for females only, having smoked tobacco products:

(a)          in an amount of at least 5 pack-years before the clinical worsening of hypogonadism; and

(b)          if smoking has ceased before the clinical worsening of hypogonadism, then that worsening occurred within 10 years of cessation;

Note: one pack-year is defined in the Schedule 1 - Dictionary.

(59)      for males only, having alcohol use disorder before the clinical worsening of hypogonadism;

(60)      for females only, being underweight for at least the 5 years before the clinical worsening of hypogonadism;

Note: being underweight is defined in the Schedule 1 - Dictionary.

(61)      inability to obtain appropriate clinical management for hypogonadism.

9               Relationship to service

(1)          The existence in a person of any factor referred to in section 8, must be related to the relevant service rendered by the person.

(2)          The factors set out in subsections 8(31) to 8(61) apply only to material contribution to, or aggravation of, hypogonadism where the person's hypogonadism was suffered or contracted before or during (but did not arise out of) the person's relevant service.

10           Factors referring to an injury or disease covered by another Statement of Principles

In this Statement of Principles:

(1)          if a factor referred to in section 8 applies in relation to a person; and

(2)          that factor refers to an injury or disease in respect of which a Statement of Principles has been determined under subsection 196B(3) of the VEA;

then the factors in that Statement of Principles apply in accordance with the terms of that Statement of Principles as in force from time to time.

Schedule 1 - Dictionary  

Note:               See Section 5

1               Definitions

In this instrument:

                             abnormality of kidney structure or function means:

(a)          having a glomerular filtration rate of less than 60 mL/min/1.73 m2; or

(b)          having kidney damage, as evidenced by renal biopsy, imaging studies, albuminuria, urinary sediment abnormalities or other markers of abnormal renal function; or

(c)          having had a kidney transplant.

                             active epilepsy means having at least one epileptic seizure per year.

                             being underweight means having a Body Mass Index (BMI) of 18.5 or less.

Note: BMI is also defined in the Schedule 1 - Dictionary.

                             BMI means W/H2 where:

(a)          W is the person's weight in kilograms; and

(b)          H is the person's height in metres.

                             chronic kidney disease means an abnormality of kidney structure or function that has been present for at least 3 months.

Note: abnormality of kidney structure or function is also defined in the Schedule 1 - Dictionary.

                             fumes means combustion products, aerosols, vapours or dust arising through industrial processes or from workplace practices that involve the refining, manufacture or use of the stated material.

                             hypogonadism—see subsection 6(2).

                             immune checkpoint inhibitor means a form of cancer immunotherapy that uses monoclonal antibodies targeting the immune checkpoint proteins. Examples include ipilumab, tremelimumab, nivolumab and pembrolizumab.

                             infertility means inability to conceive a pregnancy after 12 months of unprotected sexual intercourse, use of assisted reproductive technology or azoospermia in males.

                             MRCA means the Military Rehabilitation and Compensation Act 2004.

                             one pack-year means the amount of tobacco consumed in smoking 20 cigarettes per day for a period of 1 year, or an equivalent amount of tobacco products.

Note 1: An equivalent amount of tobacco products is 7,300 grams of smoking tobacco by weight, either in cigarettes, pipe tobacco or cigars, or a combination of same. For pipe tobacco, cigars or combinations of multiple tobacco types, 1 gram of tobacco is considered to be equal to one cigarette.

Note 2: Pack-years are calculated by dividing the number of cigarettes smoked per day by 20 and multiplying this number by the number of years the person has smoked. For example, smoking 10 cigarettes per day for 10 years is equal to 5 pack-years, and smoking 40 cigarettes per day for 10 years is equal to 20 pack-years.

                             relevant service means:

(a)          eligible war service (other than operational service) under the VEA;

(b)          defence service (other than hazardous service and British nuclear test defence service) under the VEA; or

(c)          peacetime service under the MRCA.

Note: MRCA and VEA are also defined in the Schedule 1 - Dictionary.             

                             Specified List 1 of drugs means:

(a)          alkylating agents including busulphan, carmustine, chlorambucil, cyclophosphamide, dacarbazine, lomustine, melphalan (phenylalanine mustard), nitrogen mustard (mechlorethamine), procarbazine and ifosfamide (isophosphamide);

(b)          anthracycline antibiotics including daunorubicin, doxorubicin, epirubicin and idarubicin;

(c)          ibiraterone;

(d)          platinum compounds including cisplatin and carboplatin.

                             Specified List 2 of drugs means:

(a)          androgens;

(b)          antipsychotics;

(c)          ketoconazole for males only;

(d)          opioids;

(e)          progestins for males only;

(f)           sirolimus for males only; or

(g)          steroidal antiandrogens (including cyproterone acetate) for males only.

                             specified list of chemical agents means:

(a)          2-bromopropane; or

(b)          dibromochloropropane for males only.

                             specified list of infiltrative diseases means:

(a)          amyloidosis;

(b)          endometriosis;

(c)          haemochromatosis;

(d)          a primary or secondary malignant neoplasm; or

(e)          sarcoidosis.

                             specified list of metals means:

(a)          cadmium;

(b)          lead; or

(c)          mercury.

                             terminal event means the proximate or ultimate cause of death and includes the following:

(a)           pneumonia;

(b)           respiratory failure;

(c)           cardiac arrest;

(d)           circulatory failure; or

(e)           cessation of brain function.

                             VEA means the Veterans' Entitlements Act 1986.