Secondary Amenorrhoea — DVA claim example

Diagnostic Assessment — Secondary Amenorrhoea

Example 1 of 1 · fictitious patient (Veteran CT)

Diagnostic Assessment

Secondary Amenorrhoea

No Statement of Principles applies to this condition (non-SOP claim).

ADF History

Veteran CT, date of birth 19 January 1992, Australian Army, Combat Medic, enlisted 06 February 2011, medically discharged 15 November 2019. Operational service: Afghanistan, 15 October 2012 to 30 April 2013 (warlike); Iraq, 10 November 2015 to 25 June 2016 (warlike).

Occupational History

As a combat medic the veteran provided emergency and primary care in garrison, in the field and on deployment, including resuscitation of trauma casualties, while meeting the physical standards of a combat soldier with load carriage, running and field training. Deployed role 2 duties involved long shifts in extreme heat, irregular meals and sleep, and repeated exposure to mass casualty events and indirect fire.

Medics are at high risk of psychological trauma from treating severely injured and dying casualties. Women in physically demanding military roles are recognised to be at increased risk of low energy availability, weight loss and functional hypothalamic amenorrhoea, and menstrual suppression with long-acting progestogens is commonly used for deployment.

History

Veteran CT, a combat medic in the Australian Army, developed secondary amenorrhoea on 02 March 2016 during warlike service in Iraq, after a moderate traumatic brain injury in 2015, risperidone treatment for posttraumatic stress disorder, intensive training with low energy availability, weight loss and a mass casualty event. The amenorrhoea worsened in 2017, with a further fall in oestradiol and bone loss.

Timeline

• 14 Mar 2014 — A psychiatrist diagnosed posttraumatic stress disorder related to the veteran's warlike service in Afghanistan from October 2012 to April 2013, where she treated multiple combat casualties. Her menstrual cycles were recorded as regular, every 28 to 30 days, since menarche at 13. "PTSD, cycles regular 28-30 days"
• 22 Jun 2015 — The veteran was a passenger in a military vehicle that rolled over on a field exercise. She lost consciousness for about 40 minutes, had a Glasgow Coma Scale score of 11 and three days of post-traumatic amnesia, and fractured her right clavicle. CT showed a right frontal contusion. Tramadol was started for persisting shoulder pain on 18 August 2015, and risperidone 2 mg at night on 04 August 2015 for worsening nightmares. "moderate TBI, clavicle fracture"
• 28 Oct 2015 — At her pre-deployment medical the veteran weighed 62.0 kg, BMI 22.0, and reported regular menses. She had had a hysteroscopic polypectomy with endometrial curettage on 12 August 2015 and depot medroxyprogesterone 150 mg on 20 October 2015 for menstrual suppression. Free T4 was low at 8.9 pmol/L with a TSH of 1.2 mU/L, but no follow-up was arranged. "fit to deploy, FT4 8.9"
• 14 Jan 2016 — During warlike service in Iraq the veteran treated eleven casualties after an insurgent attack on Iraqi trainees at the base, two of whom died under her care. The mental health team recorded acute stress symptoms on 20 January 2016. She was completing two physical training sessions a day and 12-hour shifts. Her last menstrual period began on 03 February 2016. "mass casualty event, acute stress"
• 14 Jun 2016 — The veteran reported to the role 2 medical officer that she had had no menstrual period since early February 2016, with hot flushes, poor sleep and fatigue. A pregnancy test was negative. Weight 54.0 kg, BMI 19.1. A deployed dietitian had calculated her energy availability at 22 kcal/kg fat-free mass/day in February 2016. Referral on return to Australia was arranged. "no menses since February"
• 05 Jul 2016 — After her return to Australia, bloods showed LH 1.1 IU/L, FSH 2.4 IU/L, oestradiol 140 pmol/L, prolactin 78 micrograms/L, free T4 8.1 pmol/L and TSH 1.0 mU/L, with a negative pregnancy test. An endocrinologist diagnosed secondary amenorrhoea of hypothalamic and pituitary origin with central hypothyroidism and drug-induced hyperprolactinaemia. MRI of the pituitary was normal. A progestogen challenge produced a withdrawal bleed. "hypogonadotrophic, prolactin 78"
• 08 Sep 2016 — A gynaecologist performed hysteroscopy, which showed grade I intrauterine adhesions that were divided, with a thin endometrium. The diagnosis of secondary amenorrhoea was confirmed. Dietetic support, a review of risperidone and hormone replacement were recommended, but no dietitian was available at her base and psychiatric review was delayed. "secondary amenorrhoea, mild adhesions"
• 14 Aug 2017 — After four months of selection-course training with low energy availability, further weight loss to 52.5 kg and an increase in risperidone to 4 mg, oestradiol had fallen to below 50 pmol/L, prolactin had risen to 112 micrograms/L and a repeat progestogen challenge produced no bleed. Bone densitometry on 21 August 2017 showed a lumbar spine Z-score of -2.3, and she developed a tibial stress fracture. "oestradiol <50, failed progestogen challenge"

Symptoms

At onset the veteran's periods stopped, and over the following months she had hot flushes, night sweats, poor sleep, fatigue, reduced libido and vaginal dryness. The symptoms worsened in 2017, with more frequent hot flushes, low mood, a tibial stress fracture and reduced bone density.

She now reports continuing amenorrhoea controlled only with hormone replacement, anxiety about her fertility, low mood and reduced exercise tolerance, and she is being followed for low bone density.

Imaging

• 22 Jun 2015 — CT brain: "Small right frontal haemorrhagic contusion without mass effect."
• 05 Jul 2016 — MRI pituitary with gadolinium: "Normal pituitary gland and stalk. No adenoma."
• 12 Jul 2016 — Pelvic ultrasound (transvaginal): "Thin endometrium measuring 3 mm. Ovaries of normal size with few small follicles; no polycystic morphology."
• 21 Aug 2017 — Dual-energy X-ray absorptiometry: "Lumbar spine Z-score -2.3 and femoral neck Z-score -1.9, low bone density for age."

Onset Date

The most likely date of onset of this condition is 02 Mar 2016.

At that date the veteran was on warlike service in Iraq as a combat medic at a role 2 facility, completing two physical training sessions a day and 12-hour shifts in extreme heat. Her last menstrual period had begun on 03 February 2016, and her next period, due on 02 March 2016, did not occur.

This date is appropriate because she had regular 28 to 30 day cycles to February 2016, recorded at her pre-deployment medical, and her periods did not return after 02 March 2016. She first reported the amenorrhoea on 14 June 2016, when it had lasted more than three months, and the diagnosis was confirmed after investigation in July 2016. The date falls within her warlike deployment.

For the low energy availability and opioid factors, the 3 months before onset run from 02 Dec 2015 to 02 Mar 2016, during which she trained intensively with an energy availability of about 22 kcal/kg fat-free mass/day and took tramadol daily. For weight loss and severe stress, the 6 months before onset run from 02 Sep 2015 to 02 Mar 2016, covering her 12.1 per cent weight loss and the mass casualty event of 14 Jan 2016. For the traumatic brain injury, medroxyprogesterone and intrauterine surgery factors, the 12 months before onset run from 02 Mar 2015 to 02 Mar 2016, covering the injury of 22 Jun 2015, the curettage of 12 Aug 2015 and the injection of 20 Oct 2015. Risperidone was taken from 04 Aug 2015, more than 4 weeks before onset, and central hypothyroidism was documented on 28 Oct 2015.

For the worsening factors, the documented worsening is 14 Aug 2017. The 3 months before it run from 14 May 2017 to 14 Aug 2017, during which she trained with low energy availability, and the 6 months before it run from 14 Feb 2017 to 14 Aug 2017, during which she lost 6.3 per cent of her body weight. Risperidone 4 mg was taken from 06 Mar 2017, and the recommended dietetic and psychiatric management was not available from September 2016.

1. What is the formal diagnosis of the condition claimed above?

The formal diagnosis is Secondary Amenorrhoea (ICD-10-AM N91.1), of functional hypothalamic and pituitary origin with drug-induced hyperprolactinaemia and a minor uterine component. No Statement of Principles has been determined for secondary amenorrhoea.

Secondary amenorrhoea is the absence of menstruation for three months or more in a woman who previously had regular cycles, or six months in one with irregular cycles, after pregnancy has been excluded. It results from disruption of the hypothalamic-pituitary-ovarian axis, from hyperprolactinaemia, thyroid disease, ovarian failure or uterine scarring. Functional hypothalamic amenorrhoea, from low energy availability, weight loss and psychological stress, is common in women in physically demanding occupations. Prolonged oestrogen deficiency causes vasomotor symptoms, bone loss and stress fractures, and affects fertility and mood.

The condition began on 02 March 2016 during warlike service in Iraq, was confirmed on investigation in July and September 2016 and worsened by August 2017.

2. For each diagnosis identified, please also provide the following dates:

When did the veteran first experience symptoms attributable to this condition?

02 March 2016.

When did the veteran first present to a health / medical provider for this condition?

14 June 2016.

When was the condition confirmed / formally diagnosed?

05 July 2016.

When did the veteran first present to you (or your practice) for this condition?

22 August 2025.

3. How was this diagnosis confirmed? i.e. what were the key symptoms and signs, investigation results, specialist opinions?

The diagnosis was confirmed by an endocrinologist on 05 July 2016: the veteran had had no menses for four months after previously regular cycles, pregnancy was excluded, and investigations showed low gonadotrophins, a low oestradiol, hyperprolactinaemia and central hypothyroidism, with a normal pituitary MRI and no polycystic ovarian morphology. This establishes secondary amenorrhoea of hypothalamic and pituitary origin. Hysteroscopy on 08 September 2016 showed minor adhesions that did not account for the amenorrhoea alone.

The worsening was confirmed on 14 August 2017 by a fall in oestradiol to below 50 pmol/L, a rise in prolactin, a negative progestogen challenge and low bone density on DXA.

4. What do you consider to be the cause(s) of the condition in this veteran? Give consideration to constitutional and common risk factors, pre-existing injuries or diseases, and occupational or lifestyle risks, as well as direct causative mechanisms.

No Statement of Principles has been determined by the Repatriation Medical Authority for secondary amenorrhoea. The claim is therefore decided on the sound medical-scientific evidence of what causes the condition, without the limits a Statement of Principles would impose. The recognised causes below are drawn from that evidence and phrased in the same way as Statement of Principles factors.

Legislation: the clinical onset of this condition was on 02 March 2016, after 1 July 2004, during warlike service in Iraq. This is a Military Rehabilitation and Compensation Act 2004 (MRCA) claim. Because the onset occurred on warlike service, the reasonable hypothesis standard of proof applies; the balance of probabilities standard applies to peacetime service, which covers the injury and treatments in Australia in 2015 and the worsening in 2017. Each cause must be related to the person's service. Under the beneficial approach required by the legislation, the absence of documentation does not mean that an event or exposure did not occur: lack of evidence is not evidence of lack.

Recognised causes on the medical-scientific evidence (no Statement of Principles)

Causative factors

Cause 1: undertaking strenuous physical activity with low energy availability, being an energy intake of less than 30 kilocalories per kilogram of fat-free mass per day after exercise energy expenditure, for at least the 3 months before the clinical onset of secondary amenorrhoea; — MET

- On deployment to Iraq from 10 November 2015 the veteran completed two physical training sessions a day, including 50 to 60 kilometres of running a week, on top of 12-hour shifts at the role 2 facility in temperatures above 40 degrees. A deployed dietitian's assessment on 22 February 2016 calculated her energy availability at about 22 kilocalories per kilogram of fat-free mass per day, with ration-pack and dining-facility intake well short of expenditure, and documented the same pattern from mid-November 2015. Low energy availability was therefore present throughout the 3 months before onset, from 02 December 2015 to 02 March 2016. Low energy availability suppresses hypothalamic gonadotrophin-releasing hormone pulsatility and is the commonest cause of amenorrhoea in military women.

Cause 2: losing at least 10 per cent of body weight within the 6 months before the clinical onset of secondary amenorrhoea; — MET

- The veteran weighed 62.0 kg at her pre-deployment medical on 28 October 2015 and 54.5 kg at the role 2 facility on 26 February 2016, a loss of 7.5 kg or 12.1 per cent, all within the 6 months before onset, from 02 September 2015 to 02 March 2016. Her BMI fell from 22.0 to 19.3. The weight loss followed the training load, heat, reduced appetite and long shifts on warlike service.

Cause 3: experiencing a severe psychological stressor within the 6 months before the clinical onset of secondary amenorrhoea; — MET

- On 14 January 2016 the veteran, as the duty medic, treated eleven casualties after an insurgent attack on Iraqi trainees at the base. Two died under her care, and she was exposed to indirect fire on at least six further occasions in January and February 2016. The mental health team recorded acute stress symptoms on 20 January 2016. These events were 1 month and 17 days before onset, within the 6 months from 02 September 2015 to 02 March 2016. Severe stress raises cortisol and corticotrophin-releasing hormone, which suppress the reproductive axis.

Cause 4: taking a drug which causes hyperprolactinaemia, including risperidone, for at least the 4 weeks before the clinical onset of secondary amenorrhoea; — MET

- A psychiatrist prescribed risperidone 2 mg at night on 04 August 2015 for posttraumatic stress disorder with nightmares and agitation, related to her warlike service in Afghanistan in 2012 to 2013. She took it every night through her deployment and up to and beyond the onset, a period of 7 months, well over the 4 weeks required. Serum prolactin was 78 micrograms/L on 05 July 2016. Risperidone blocks dopamine receptors in the pituitary and is a leading cause of drug-induced hyperprolactinaemia and amenorrhoea.

Cause 5: having a traumatic brain injury within the 12 months before the clinical onset of secondary amenorrhoea; — MET

- On 22 June 2015 the veteran was a passenger in a military vehicle that rolled over during a field exercise in Queensland. She lost consciousness for about 40 minutes, had a Glasgow Coma Scale score of 11 and post-traumatic amnesia for three days, and CT showed a small right frontal contusion. A moderate traumatic brain injury was diagnosed. This was 8 months and 9 days before onset, within the 12 months from 02 March 2015 to 02 March 2016. Pituitary testing in July 2016 showed low gonadotrophins and central hypothyroidism consistent with post-traumatic hypopituitarism.

Cause 6: having hypothyroidism at the time of the clinical onset of secondary amenorrhoea; — MET

- Pre-deployment bloods on 28 October 2015 showed a free T4 of 8.9 pmol/L, below the reference range, with an inappropriately normal TSH of 1.2 mU/L, but this was not followed up before she deployed. On 05 July 2016 the free T4 was 8.1 pmol/L with a TSH of 1.0 mU/L, and an endocrinologist diagnosed central hypothyroidism after the traumatic brain injury. The hypothyroidism was therefore present at onset on 02 March 2016.

Cause 7: receiving an injection of depot medroxyprogesterone acetate within the 12 months before the clinical onset of secondary amenorrhoea; — MET

- On 20 October 2015 the garrison health centre gave the veteran depot medroxyprogesterone acetate 150 mg by intramuscular injection for menstrual suppression during deployment, as commonly offered to deploying women. This was 4 months and 11 days before onset, within the 12 months from 02 March 2015 to 02 March 2016. Depot medroxyprogesterone suppresses ovulation and can cause prolonged amenorrhoea after the last injection.

Cause 8: taking opioid medication daily for at least the 3 months before the clinical onset of secondary amenorrhoea; — MET

- The veteran fractured her right clavicle in the vehicle rollover of 22 June 2015 and was left with chronic shoulder pain. Slow-release tramadol 200 mg daily was prescribed from 18 August 2015 and continued through her deployment, so she took an opioid daily throughout the 3 months before onset, from 02 December 2015 to 02 March 2016. Opioids suppress hypothalamic gonadotrophin-releasing hormone and cause hypogonadism.

Cause 9: having intrauterine surgery, including curettage of the endometrium, within the 12 months before the clinical onset of secondary amenorrhoea; — MET

- On 12 August 2015 a gynaecologist performed hysteroscopic removal of an endometrial polyp with curettage of the endometrium for heavy menstrual bleeding, 6 months and 19 days before onset, within the 12 months from 02 March 2015 to 02 March 2016. Hysteroscopy on 08 September 2016 showed grade I intrauterine adhesions, a recognised consequence of curettage that reduces the endometrial response to hormones.

Worsening factors

Worsening 1: undertaking strenuous physical activity with low energy availability for at least the 3 months before the clinical worsening of secondary amenorrhoea; — MET

- From April 2017 the veteran trained for a physically demanding selection course, running 70 kilometres a week and completing loaded marches, and a sports dietitian on 31 July 2017 calculated her energy availability at about 20 kilocalories per kilogram of fat-free mass per day. Low energy availability continued throughout the 3 months before the documented worsening, from 14 May 2017 to 14 August 2017.

Worsening 2: losing at least 5 per cent of body weight within the 6 months before the clinical worsening of secondary amenorrhoea; — MET

- The veteran's weight fell from 56.0 kg on 20 February 2017 to 52.5 kg on 14 August 2017, a loss of 6.3 per cent within the 6 months before the worsening, from 14 February 2017 to 14 August 2017, with her BMI falling to 18.6.

Worsening 3: taking a drug which causes hyperprolactinaemia, including risperidone, for at least the 4 weeks before the clinical worsening of secondary amenorrhoea; — MET

- Risperidone was increased to 4 mg at night on 06 March 2017 for worsening posttraumatic stress disorder and was taken every night throughout the months before the worsening. Serum prolactin rose from 78 to 112 micrograms/L on 14 August 2017.

Worsening 4: inability to obtain appropriate clinical management for secondary amenorrhoea. — MET

- Her low free T4 in October 2015 was not followed up before deployment, and in theatre there was no gynaecology or endocrinology service, so the amenorrhoea was not investigated until July 2016. After diagnosis, the endocrinologist recommended dietetic support, a review of risperidone and hormone replacement in September 2016, but the veteran's base had no dietitian and her psychiatric review to change risperidone was not available for six months. The amenorrhoea worsened with a fall in oestradiol and bone loss. Under Brew v Repatriation Commission (1999) this is an inability to obtain appropriate clinical management.

The % contribution of the causes is 100% and significant.

Sequelae

The secondary amenorrhoea is a sequela of the veteran's accepted conditions: the moderate traumatic brain injury of June 2015 with post-traumatic hypopituitarism, posttraumatic stress disorder and its treatment with risperidone, and the chronic shoulder pain treated with tramadol. The low bone density and tibial stress fracture are sequelae of the amenorrhoea.

Unintended Consequence

Met. The hyperprolactinaemia from risperidone, the hypogonadism from tramadol, the prolonged suppression from depot medroxyprogesterone given for deployment and the intrauterine adhesions after curettage are unintended consequences of medical treatment provided and paid for by the Commonwealth while the veteran was serving (section 6A of the DRCA and the equivalent provisions of the MRCA).

Inability to Attain Appropriate Medical Management

MET. The veteran's low free T4 in October 2015 was not followed up before deployment, and in Iraq there was no access to gynaecology or endocrinology, so her amenorrhoea was not investigated until July 2016. After diagnosis, the recommended dietetic support and psychiatric review of risperidone were not available at her base for six months, and the amenorrhoea worsened with oestradiol falling below 50 pmol/L and bone loss. Applying the objective and subjective tests in Brew v Repatriation Commission (Full Federal Court, 10 September 1999, Merkel J), operational and administrative barriers that prevent investigation and prescribed treatment amount to an inability to obtain appropriate clinical management.

5. Please provide a Health Summary and a medication / prescribing history.

See attached report.

References

1. 14 Mar 2014, Psychiatric assessment, Consultant psychiatrist
2. 22 Jun 2015, Hospital admission and CT report, Emergency physician and radiologist
3. 12 Aug 2015, Operation report, Gynaecologist
4. 28 Oct 2015, Pre-deployment medical and pathology, Medical Officer
5. 20 Jan 2016, Mental health record, Deployed psychologist, Iraq
6. 22 Feb 2016, Dietetic assessment, Deployed dietitian, Iraq
7. 14 Jun 2016, Role 2 health record, Medical Officer, Iraq
8. 05 Jul 2016, Endocrinology consultation and MRI pituitary report, Endocrinologist and radiologist
9. 08 Sep 2016, Hysteroscopy report, Gynaecologist
10. 14 Aug 2017, Endocrinology review and pathology, Endocrinologist
11. 21 Aug 2017, Bone densitometry report, Radiologist
12. Repatriation Medical Authority: no Statement of Principles determined for secondary amenorrhoea; causes drawn from the sound medical-scientific evidence