Impact of childhood exogenous hormones on mood

To the Editor

Marfan’s syndrome is a rare connective tissue condition that occurs when a mutated FBN1 gene is inherited in an autosomal dominant manner or arises as a new mutation. Individuals with Marfan’s experience a range of symptoms including bone overgrowth, joint deformity, myopia and aortic dilation and dissection (Summers et al., 2012).

Although not pathological, tall stature resulting from Marfan can be managed with exogenous hormones during childhood. While effective in decreasing growth, little literature exists regarding the impact of this treatment on mood (Hannema and Savendahi, 2016).

We first met Donna (not her real name), a 38-year-old working mother with Marfan’s syndrome, 4 months after the birth of her son, who was conceived via in vitro fertilisation (IVF). She presented in response to a drastic mood shift during pregnancy. Having suffered from major depressive disorder for 20 years, Donna described ‘seeing the world in colour’ for the first time over the course of her pregnancy, which returned to ‘grey’ 1-month post-partum.

As a child, Donna was given exogenous oestradiol and progesterone from 8 to 12 years old, to avoid tall stature. The hormones were abruptly ceased, and at the age of 12 years, Donna suffered menopause-like symptoms. Treatment was then re-commenced and appropriately titrated down. Throughout her teenage years, she experienced low mood, which worsened during premenstrual periods. At the age of 18 years, Donna was diagnosed with major depressive disorder and commenced on lifelong antidepressants.

We believe that Donna has major depressive disorder, with sensitivity to hormonal fluctuations. The disruption to Donna’s hypothalamic–pituitary–gonadal (HPG) pathway with exogenous hormones at a physiologically formative time is likely to have contributed to this. Early-life trauma experiences exacerbated this susceptibility.

Donna also experiences fortnightly migraines with aura, but no neurological symptoms. In consultation with neurologists and after discussion with Donna regarding the risks, the contraceptive pill ‘Zoely’ (estradiol hemihydrate + nomegestrol acetate) was prescribed. This hormonal therapy minimizes the hormonal fluctuations that Donna experiences by providing an increased, consistent dose of oestrogen, which creates a steadier concentration through negative feedback with the HPG axis.

After 2 months of treatment, Donna has noted significant improvement in her mood, as well as alleviation of her insomnia and is experiencing far fewer migraines.

Age	Event
8–12	Given exogenous oestradiol and progesterone
12	Exogenous hormones ceased – experiences induced menopause
12	Hormones restarted and weaned
12–18	Mood symptoms – irritability, depression, put down to ‘teenage moodiness’
18	First antidepressant – Citalopram, life ‘grey’ rather than ‘black’
37	Commenced on IVF treatment (hormonal therapy) – improvement in mood
38	Son born – decline in mood over the following month with a return to baseline
4 months post birth	First consult in clinic – ‘Zoely’ commenced
6 months post birth	Improvement in symptoms