Elsevier

Psychoneuroendocrinology

Volume 36, Issue 7, August 2011, Pages 1005-1009
Psychoneuroendocrinology

Changes in the sleep electroencephalogram (EEG) during male to female transgender therapy

https://doi.org/10.1016/j.psyneuen.2010.12.014Get rights and content

Summary

Steroids, including estrogens, participate in sleep regulation. For example estrogen replacement therapy improved sleep quality in postmenopausal women. Patients, who undergo a cross-gender hormone therapy, receive high doses of estrogens. The effects of this treatment on sleep are unknown. To clarify this issue, we examined seven male to female transsexual patients (age range 31–44 years, mean ± SD 35.9 ± 4.2 years). The patients spent two nights on 2 separate occasions in our sleep laboratory. The first night of each session served for adaptation to laboratory conditions. In the second night sleep electroencephalogram [EEG] was recorded from 2300 h to 0700 h. The first examination was performed before and the second about 3 months after initiation of cross-gender hormone therapy with a dose of 80–100 mg estrogen applied every 2 weeks. Additionally patients were treated with a starting dose of the anti-androgen cyproteronacetate of 100 mg/day and after about 6 weeks with a maintenance therapy of 50 mg/d in order to suppress androgenic effects. Statistical analysis was performed with the Wilcoxon rank test. Under this estrogen therapy we found a significant increase in stage 1 sleep during the whole night (at baseline [b]: 33.29 ± 9.94 min; treatment [t]: 51.57 ± 24.26 min; p < 0.05) Beta activity in nonREM sleep was significantly increased (p = 0.02) during hormone therapy compared to before treatment. Other sleep EEG parameters showed no significant changes. Administration of estrogen and anti-androgens in male to female transsexual patients had only a small influence on sleep EEG, with an increase in the duration of shallow sleep.

Introduction

Estrogens modulate the sleep electroencephalogram (EEG). In transgender therapy of male to female transsexual patients high doses of sexual steroids are given. The effects of this treatment on sleep EEG are unknown so far.

Sex differences in sleep electroencephalogram (EEG) are reported by different groups. Animal studies gave already good hints for sex related differences in sleep architecture. For example, in one study the sleep of intact and gonadectomized female and male C57BL/6J (B6) mice was investigated (Paul et al., 2006). This strain is useful for examining sex-related differences in sleep since the females show very little changes in sleep distribution across the estrous cycle (Koehl et al., 2003). The amount of wakefulness was higher and the amount of NonREM sleep was lower in the intact female than the intact male B6 mice. Ovariectomy resulted in a decrease in wake and a corresponding increase in non-rapid-eye-movement (NonREM) sleep. This finding suggests that sex differences in intact animals contribute to gonadal hormones. Male rats displayed more REM sleep than female rats in a 12:12 h light/dark cycle and ovariectomy lead to an increase of REM sleep during the dark phase in female rats eliminating the sex difference during the night (Fang and Fishbein, 1996). Sleep also varies across the estrous cycle. REM sleep is decreased particularly during the dark phase in female rats during proestrus, when β-estradiol plasma concentrations are high (review by Manber and Armitage, 1999).

In human studies sex differences are already found in neonatal and prepubertal children (Thordstein et al., 2006, Hatzinger et al., 2008) obviously independently from gonadal steroids. In contrast these hormones participate in sleep differences of adult subjects and of menopausal women and ageing men. In premenopausal women Lee et al. (1990) found REM latency to be shorter in the luteal phase. Driver et al. (1996) reported a close relation between menstrual cycle and sleep in premenopausal women. In young healthy women EEG power density in the 14.25–15.0 Hz band exhibits large variations across the menstrual cycle. It decreases during the follicular phase, when estrogen increases. Also in elder subjects sex differences in sleep are described. Van den Berg et al. (2009) found women reporting a shorter sleep time than men, but found poorer actigraphic sleep measures in men than in women. During the menopause in women a rather sharp decline in the sigma frequency range was observed, whereas in men sigma activity decreased more gradually during ageing (Ehlers and Kupfer, 1997). Sleep disturbances are a frequent symptom in postmenopausal women. Whereas hot flashes, which cause short-term awakenings (Erlik et al., 1981) contribute to this complain, impaired sleep was reported also in postmenopausal women without hot flashes.

Administration of reproductive steroids to women in oral contraceptive formulations or hormone replacement therapy has been shown to influence sleep. Women taking oral contraceptives containing estrogen and a progestin have less slow wave sleep, more stage 2 sleep, and more REM sleep than naturally-cycling women (Driver et al., 1996). Estrogen replacement therapy in peri- and postmenopausal women decreased sleep latency and increased total sleep time in some (review by Manber and Armitage, 1999) but not all (Antonijevic et al., 2000b) studies. REM sleep was increased during the total night (Thomson and Oswald, 1977, Scharf et al., 1997) or during the first two sleep cycles (Antonijevic et al., 2000b) respectively. In the latter study also time awake was reduced during this interval. Furthermore the normal decrease in slow-wave sleep and EEG delta activity and sigma activity from the first to the second half of the night were increased after estrogen replacement therapy (Antonijevic et al., 2000b). Additionally a sexually dimorphic response to stimulation with GHRH was described which strongly suggests an additional control of sleep regulatory mechanisms by sex hormones (Antonijevic et al., 2000a).

Transsexual patients who undergo cross-gender therapy (CGT) from male to female receive high dosages of estrogens. It is well established that changes of behaviour occur during this treatment. Its effect on sleep EEG is unknown so far. Our aim was to investigate patients longitudinally before and after high dose transgender therapy to observe the effects of high doses of female sex hormones and their influence on male sleep EEG.

Section snippets

Subjects

Seven patients with transsexualism from male to female, who received unphysiologically high doses of estrogens and antiandrogens during their cross-gender therapy, were investigated. Age range was from 31 to 44 years (mean age 35.9 ± 4.2 years).

All subjects met the following inclusion criteria: Medical history without major or chronic diseases (e.g. diabetes, heart failure, hepatitis, etc.), no previous psychiatric or chronic neurological disorder, normal physical examination including a complete

Results

Results of conventional sleep EEG analysis are given in Table 1.

After 3 months of CGT, none of the sleep continuity variables (total sleep time, time in bed, sleep onset latency, sleep period time, number of awakenings, number of stage shifts) showed a significant difference from the baseline assessment.

There was only a significant increase of sleep stage 1 [baseline [b]: 33.2 ± 9.9 min; treatment [t]: 51.5 ± 24.2 min; p = 0.02], but the amount of the other sleep stages and of REM sleep was not

Discussion

The major findings of our study are increases of sleep stage 1 and of EEG beta activity during the total night after male to female transgender therapy.

Whereas subjects were treated with unphysiological high doses of estrogens and antiandrogenes only moderate sleep EEG changes were observed. According to conventional sleep EEG variables sleep tended to become shallower after therapy as sleep stage 1 increased during the whole night. This finding points to a weak sleep-impairing effect of

Role of funding source

None.

Conflict of interest

Harald Murck received grants from Hermes Arzneimittel, Grosshesselohe, Germany. He was employed by Lichtwer Pharma (now Cassella), Laxdale (now Amarin), Novartis, US and is now employed by Bristol-Myers Squibb, USA. He holds stocks from Bristol-Myers Squibb as part of his compensation.

Axel Steiger received a grant from Dr. Kade, Berlin, Germany.

Acknowledgement

We thank Dr. Z. Koralyi for her help in recruiting patients.

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