Perimenopausal in psychiatry, very interesting subject

1. Psychotic and Mood
Disorders
Associated with the
Perimenopausal Period

2. The ‘Perimenopause’ or ‘climacteric’ is the phase
of life in the aging process of women marking the
transition from the reproductive to the nonreproductive
stage of life.
The Perimenopause is divided into the
‘menopausal transition phase’, during which most women
are aware of changes in menstrual flow and frequency,
and the ‘post menopause phase’

4. Epidemiology
 increase in somatic complaints at menopause
 complaints of mental imbalance, fatigue, depression and irritability
were most common in women who were still menstruating
 menopause-related affective disorders would present as melancholia,
and other types of affective disorders
 Women who undergo surgical menopause may exhibit more severe
vasomotor symptoms, depression, anxiety and insomnia than women
undergoing natural menopause
 more marked
 vasomotor symptoms due to the sudden dramatic change in hormone
levels

6. Role of Reproductive
Hormones
 Estrogen and progesterone have been linked to the regulation of mood in a number of different
ways
 Estrogen can lead to an increase in the density of receptors for a number of neurotransmitters.
 Estrogen enhance central noradrenaline (norepinephrine) availability, sensitize dopamine
receptors and reduce plasma monoamine oxidase (MAO) activity.
 Estrogen also cause an increase in serotonin (5-hydroxytryptamine; 5-HT) levels and increase
the density of tritiated imipramine binding sites, which influences the presynaptic uptake of
serotonin in the brain and in platelets
 Estrogen decrease during the Perimenopause could help explain the occurrence of depressive
symptoms or major depressive illness in vulnerable women.
 Estrogen influences the cognitive functioning via its effect on acetylcholine

7. Role of Reproductive Hormones
 Progesterone increases the activity of MAO, leads to decreased levels
of neurotransmitters and predispose to dysphoric moods.
 Progesterone metabolized in to a subtype of GABA, causes
somnolence, fatigue and depression
 Estrogen also play a role in psychosis.
 Antidopaminergic or Antipsychotic like action of estrogen protect
against development of Schizophrenia.

8. Aetiology
The Psychoendocrine Model
 In Perimenopause, alterations of Estradiol, Progesterone, FSH &
LSH, affect neurotransmitter activity.
 Estrogen deficiency lead to Depression & Schizophrenia in
vulnerable women.
 Changes in Thyroid Hormones leads to changes in estradiol
production > dysregulation of hypothalamic pituitary thyroid
and adrenal axes, and causes Affective disorders.

9. Aetiology
The Domino Theory
 postulates that low mood, irritability and decreased concentration
may occur as a result of the hormone-sensitive physical
complaints
 Sleep disturbance secondary to night sweats, and irritability,
discomfort and decreased self-esteem due to hot flashes, may
lead to psychological symptoms that can be confused with major
depressive disorders
 The increased sense of well-being in mildly depressed
postmenopausal women, is due to HRT

10. Aetiology
Psychosocial Factors
 Psychosocial stressors may include:
- changes in family roles
- children leaving (‘empty nest syndrome’) or returning
home
- loss of fertility
-loss of friends and relatives because of illness
and death
- decreased physical health.

11. Psychiatric Illnesses During the
Perimenopause
Affective Disorders
 Depression is commonly associated with the Perimenopause.
 an increase in agitation, initial insomnia and hypochondriasis
with higher rates of comorbid anxiety
 Women with the onset of depression during midlife may have
a poorer outcome and a more chronic course compared with
depressed men

12. Schizophreni
a
 Schizophrenia in women tends to have a different onset and course
compared with that in men
 Women tend to have a later onset of schizophrenia,shorter duration
of hospital stays and generally better treatment outcomes
 They are more vulnerable
 to exacerbations of schizophrenic illness during
 times of hormonal change including premenstrually, postpartum and
postmenopausally
 As women reach menopause, gender differences in the course and
response to treatment are lessened as the protective influences of
estrogen decrease

13. Tardive
Dyskinesia
 The risk of antipsychotic-induced tardive dyskinesia (TD) increases
with age and the prevalence is highest in women over age 70
years
 Estrogen withdrawal may contribute to the appearance of TD
 Estrogen may modulate dopamine mediated-behaviours and
protect against oxidative stress–induced cell damage caused by
long term exposure to antipsychotics.

14. Estrogen and Memory
 The women who were given estrogen had higher
scores of immediate verbal memory
 Estrogen appears to enhance short term verbal
memory
 These improvements in memory appear to be
direct effects of estrogen rather than related to
amelioration of vasomotor symptoms

15. Role of Hormone Replacement Therapy (HRT)
 women with total abdominal hysterectomy for benign disease have
shown that those treated postoperatively with estrogen or a
combined estrogen-androgen preparation had more positive moods
than a control group of untreated oophorectomised women.
 treated women felt more composed, elated and energetic
 an increased sense of wellbeing when physiological doses of
estrogen are given.
 The progesterone may mitigate the mood-enhancing effect of
estrogen
 When these hormones are given in a cyclic fashion, women may
experience a lowered mood during the progesterone phase

16. Effects of HRT in Depressed
Women
 The role of HRT in treating major depressive episodes in
Perimenopausal women has not been well studied.
 There may be improvement in peri and menopausal women
treated with transdermal estradiol therapy
 estradiol significantly improved depression scores in women
who had major or minor depression with or without hot
flashes

17. Management
 Women with affective symptoms in Perimenopause, requires
thorough evaluation of present symptoms, past psychiatric illness
and personal history.
 Perimenopause can be documented by measuring FSH & LSH
levels at different intervals.
 HRT to treat depression basing on assessment.
 Patients beliefs about fears, ageing,feminity and sexuality should
be considered.
 Attention required for patient current situation , ongoing stressors,
responsibilities, losses and illnesses.

19. Biological
Treatments
 Mild Symptoms: women experiencing mild depression with
some anxiety, insomnia, and somatic symptoms of estrogen
deficiency (such as hot flashes, night sweats and vaginal
dryness), HRT should be suggested as the first-line treatment.
 Moderate to Severe Depression: women with moderate to
severe depression or anxiety, antidepressant medication is the
treatment of choice(fluoxetine 20mg once daily, citalopram 20mg
once daily, sertraline up to 200mg once daily). if these women
also experience somatic symptoms of menopause, the use of
HRT to relieve these symptoms may also help improve their
general mood.

20. Schizophreni
a
 in postmenopausal women who have schizophrenia, HRT
may enhance the activity of antipsychotic medication.
 Younger women experience equivalent benefits of
antipsychotic drugs more quickly and at lower dosages than
men
 postmenopausal women may require the same dosages of
antipsychotic medication as men

21. Symptoms Caused by HRT
 patient who is already receiving HRT presents with mild cyclical
symptoms of depressed mood, the relationship between the
commencement of hormone use and the onset of psychological
symptoms should be evaluated.
 women who continue to have somatic symptoms may require
higher dosages of estrogen or a change to a different form of
estrogen
 Sequential HRT (14 days per month of estrogen therapy followed
by 1 week of progesterone to induce withdrawal bleeding) may
be more likely to be associated with periodic increases in
depressive and anxiety symptoms. A change to a continuous
combination therapy may be beneficial.

22. HRT Trails in Perimenopausal

23. Efficacy of Antidepressants in MDD in
Perimenopausal

24. Psychological
Treatments
 Psychological treatments may also be of help in dealing with
women who are distressed at this time of life
 For women whose anxiety and depressive
 Symptoms providing correct information and eliminating
harmful myths about the menopause, thereby decreasing
psychological symptoms
 Patient support groups can often be very
 helpful, allowing women to look at menopause in
 a more positive light

25. Conclusion
 Majority of women manage this transition without difficulty
 For some women the freedom from menstruation and pregnancy heralds a
time of increased independence and well-being
 women who do become depressed in the Perimenopause may be
particularly vulnerable to the effects of changes in gonadal hormones on
neurotransmitter levels
 psychological distress may be a function of reactions to the vasomotor
symptoms
 There is a clear evidence of the value of HRT in the prevention of
cardiovascular disease and osteoporosis in postmenopausal women
 HRT role in the treatment of depression remains more speculative
 The available evidence is insufficient for recommending any botanical or
complementary/alternative approaches for treating depression related to the
Perimenopause
 It is reasonable to recommend exercise in peri- and postmenopausal
women with depression, particularly when used in combination with
recommended psychotherapies and pharmacotherapies.