Rare cause of manic period trigger in bipolar mood disorder: testosterone replacement

Abstract

Hypogonadotropic hypogonadism is a rare congenital disorder characterised by the deficiency and the absence of puberty and infertility. It is caused by the deficient production, secretion or action of gonadotropin-releasing hormone, which is the master hormone regulating the reproductive axis. Gonadotropin-releasing hormone or gonadotropin injections and testosterone replacement therapy are required in the treatment of this disorder. Psychiatric symptoms and disorders may be seen with the use of anabolic androgenic steroids. In this case report, we present a case report in which a patient had behavioural symptoms in childhood and develops bipolar disorder after testosterone replacement therapy. This patient was reached to the remission by increasing the doses of psychiatric drugs without interfering with hormonal therapy. It should be considered that patients receiving testosterone replacement therapy may develop bipolar disorder or trigger mood changes in bipolar mood disease, so behavioural and mood state changes should be closely followed in patients who have bipolar mood disease.

Background

Hypogonadotropic hypogonadism (HH) is a disorder characterised by the deficiency and the absence of puberty and infertility. It is caused by the deficient production, secretion or action of gonadotropin-releasing hormone (GnRH), which is the master hormone regulating the reproductive axis.¹ Although it is a relatively rare endocrine disorder, the most common form of gonadotropin deficiency is congenital hypogonadotropic hypogonadism. This disorder is five times more common in males.² Testosterone replacement therapy and GnRH or gonadotropin injections are required for treatment.³ The use of exogenous testosterone causes adverse side effects such as libido increase and aggression in some cases.⁴ In this article, we present a case ofbipolar disorder manic period episode due to testosterone and human chorionic gonadotropin (hCG) replacement therapy.

Case presentation

A 25-year-old man, single, had a high school education, was presented. He had no occupation. He has a supportive parent. He reported no family history of psychiatric disorder in any first-degree relative. He applied to the psychiatric polyclinic with the complaints such as over speaking, increased activity, aggression, increase in sexual desire, spending a lot of money about 1 month.

His own psychiatric history had been benign at the age of 6 with much mobility, incompatibility, not getting along with friends, breaking windows and hitting walls. At that period, he was diagnosed with attention deficit hyperactivity disorder (ADHD), but he did not receive a treatment. However, in his teens, he has suffered from obsessive compulsive disorder (OCD) too. All diagnoses were made using Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. Central to the patients’s OCD were hoarding behaviours and cleaning rituals (eg, washing his hands or frequently changing clothes, arranging items numerous times). The OCD followed a chronic waxing pattern in which he would spend 4–8 hour in a day on his ritualistic behaviours. During the same period, he was treated by methylphenidate 18 mg/daily, escitalopram 10 mg/daily, olanzapine 5 mg/daily by considering the diagnosis of ADHD and OCD. It was observed that there was a reduction in severity of the obsessive symptoms with this treatment.

However, he reported that at the age of 17, he was readmitted to the psychiatry department because of nervousness and aggressive behaviours. So quetiapine 100 mg/daily was added to the treatment by considering that the patient has impulse control disorder. Furthermore, endocrinology consultation was asked due to the complaint made for the accompanying of delayed puberty.

On physical examination, his height was 155 cm and he weighed 70 kg, revealed small testes (volume 2–3 cm³ each) and Tanner stage 3 pubic hair. Detailed laboratory and imaging studies were performed. It was observed as follows: luteinising hormone 0.205 mIU/ml (normal range 1.7–8.6), follicle-stimulating hormone 0.817 mIU/ml (normal range 1.5–12.4), growth hormone 0.444 ng/mL (normal range 0.05–8.6), thyroid-stimulating hormone 1.55 uIU/ml (normal range 0.34–5.6), testosterone <20 ng/mL (normal range 170–810), dehydroepiandrosterone sulfate 269 ug/dL (normal range 61.2–493.6) and prolactin 8.56 ng/mL (normal range 3.5–19.4). Serum gonadotropin and testosterone concentrations were in the prepubertal range. Scrotal ultrasonography showed that the testes volume are 1.3 cm³ and 1.4 cm³ and the breast ultrasonography showed diffuse lipomatous pattern. Abdomen CT and brain MRI were normal. Luteinising hormone-releasing hormone stimulation test was done and there was no increase at 0, 30, 60 and 120 min. HH was diagnosed in the patient. The patient was treated with 1500 units of hCG three times a week and 250 units testosterone once every 3 weeks. In the third month of hormone therapy, he admitted to hospital with the diagnosis of manic episode of bipolar disorder for the first time on the symptoms such as over speaking, mobility, aggression, sexual desire increase, spending a lot of money and flight of ideas. After about 2 weeks of treatment, patient who reached the remission was discharged with valproate 1000 mg/day and risperidone 6 mg/daily. He had used the hormone drugs irregularly because they triggered irritability and manic episodes. He had two manic and three depressive periods. Two months ago on his examination of psychiatric, fast talking, flight of ideas, feeling strong and powerful, hyperactivity, elevation in mood state was found. According to DSM-V, he was completing the hypomanic episode criteria. Treatment was created as 1000 mg/day valproate, 9 mg/day risperidone, 4 mg/day biperidine and 30 mg/day aripiprazole. The patient who has benefited from the treatment is still in remission. His hormonal therapy continued as testosterone 50 mg gel once in 4 days and 1500 units of hCG once a week.

Outcome and follow-up

After the the treatment with valproate, risperidone, biperidin, aripiprazole and testosterone hormone replacement, patient have not had depression or manic period for a year.

Discussion

Hypothalamic–pituitary–adrenal (HPA) axis and end effectors play a central role in the response adaptive to various stress factors which can be internal or external, glucocorticoid hormones. This system has a strong impact on the basic functions such as brain hippocampus and cognition, memory, behaviour and mood.⁵ The disorder of the HPA axis is one of the most commonly described changes associated with symptoms of mood disorders and other neuropsychiatric disorders. Hypogonadism symptoms are characterised by clinical findings such as mood changes, sleep disturbances, libido reduction, low energy, weakness, muscle weakness, muscle aches, poor concentration, poor memory and infertility.⁶ Complaints of behaviour disorders starting in childhood which cause frequent psychiatric admission may be associated with deterioration in the functioning of the HPA hormonal axis in the case.

Hypogonadism is associated with increased risk of type II diabetes, obesity, dyslipidaemia, obstructive sleep apnoea, coronary artery disease and osteoporosis. Testosterone replacement therapy is a safe and effective therapy for the prevention of morbidity associated with this condition.⁶ Literature increasing on the use of androgenic anabolic steroids makes us think some users may develop aggression such as mood disorder, hypomania, restlessness and depressive episodes.⁷ It can be often seen that athletes using anabolic androgenic steroids have psychiatric symptoms and disorders. Mood and psychotic disorders as well as mostly somatoform and eating disorders can be seen.⁸ There are rarely hypomania and bipolarity cases reported after the use of testosterone.^{9 10} It is important how the treatment of the patient can be sustained after receiving bipolar disorder diagnosis.

Testosterone replacement therapy adversely affected the course of bipolar disorder and deteriorated the patient’s adherence to treatment. In a similar case which has been reported, it has been passed to treatment with topical testosterone instead of monthly intramuscular injections.⁹ We reached the remission on this patient by increasing drug doses without any interruption to the testosterone treatment dose the patient received.

The diagnosis of HH and bipolar disorder in this patient is important for his future health. When diagnosed early for HH, comorbidities like type II diabetes, obesity, dyslipidaemia, obstructive sleep apnoea, coronary artery disease and osteoporosis can be reduced or even eliminated. And also be careful about the adverse effect of testosterone replacement therapy for compliance to treatment. This case highlights the value of obtaining a detailed history and performing a thorough physical examination. This case also indicated the importance of collaboration between expertised physicians.

Learning points.

• Psychiatric symptoms and disorders may be seen with the use of anabolic androgenic steroids in patient with bipolar mood disorder.

• Testosterone replacement therapy may cause poor adherence of bipolar mood disorder treatment and may trigger manic period.

• Collaboration between expertised physicians is important to take care of the patients treatment correctly.