A few example case reports may help to illustrate the kinds of problems encountered in the clinic and how they may be dealt with.

Patient 1

A 44-year-old woman presented with an 8-month history of ‘constant premenstrual syndrome (premenstrual syndrome)’, and a 4-month history of anxiety, agitation, irritability, of feeling depressed and of rare panic attacks. She had had irregular menses for 1 year, with hot flushes and sweating for 2 months. Past history was positive for premenstrual syndrome (anxiety, irritability, crying) and postpartum depression with panic attacks. Family history was positive for left-handedness and autoimmune disorders. Treatment had included nortriptyline, clonazepam and, for 3 weeks, premarin which had increased her irritability and anxiety. Serum estradiol was 69 µg/1, (estrone level not determined) and mid-luteal progesterone was normal at 13.3 µg/1. follicle stimulating hormone was 15 IU. She was felt to have agitated depression in the setting premature perimenopause. Treatment with micronized oral progesterone 200 mg three times a day led to resolution of psychiatric symptoms (while vasomotor symptoms persisted). Hamilton Depression Rating Scale scores improved from 11 to 2, and profile of mood scale tension subscore improved from 20/36 to 9/36. Post-treatment estradiol level was 76 µg/1, progesterone 35.7 µg/1, with estradiol/progesterone ratio dropping from 0.0051 pretreatment to 0.0021 after treatment. The patient was drowsy on this dose. Drowsiness abated with progesterone dose reduction to 100 mg four times a day. The patient stopped nortriptyline and clonazepam and has remained well during a 3-year follow-up.

Patient 2

A 5 5-year-old woman was referred for a second neurological evaluation of possible dementia. She had undergone hysterectomy and bilateral oophorectomy for ovarian carcinoma 5 years previously, with no relapse. She had suffered from depression for 15 years. The depression became worse after the oophorectomy. She had passive suicidal thoughts, impaired motivation and concentration, leading to the loss of a highly demanding job. Medroxyprogesterone caused fatigue. Unsuccessful psychiatric treatments had included doxepin, imipramine and trifluoperazine. Past medical history was positive for prematurity and well-substituted hypothyroidism, premenstrual syndrome with irritability and insomnia, and postpartum depression in two out of two pregnancies, with crying and lack of energy. Examination showed the patient to be depressed and neurologically normal. Serum estradiol level was 10 µg/1, progesterone 0.4 µg/1. Within 1 week of starting treatment with Estraderm ® patch 0.05 mg twice weekly her symptoms resolved. She started a new job and discontinued imipramine and Stelazine ®. Her Hamilton Depression Rating Scale score improved from 21 pretreatment to 2. Serum estradiol increased to 92 µg/1 with unchanged progesterone level. Estradiol/progesterone ratio increased from 0.025 pretreatment to 0.23 on treatment. She has remained symptomfree for 2!/2 years.

Patient 3

A 59-year-old woman was seen because of a 14-month history of compulsive behavior (incessant apologizing for what she considered to be intrusive behavior), leading to job loss and virtual house-incarceration. She also had mild anxiety and depression. The symptoms started at the same time as sweating, hot flushes and loss of libido. Past history included 6 months of compulsive cleaning, aged 50, after the death of her brother, anorexia-bulimia at the age of 15, secondary amenorrhea, ovarian cysts and fibroids, agitation and anxiety with oral contraceptive treatment. She had not had postpartum depression or premenstrual syndrome. Her mother had suffered from depression at the time of menopause. Past unsuccessful treatment had included sertraline, loxapine and nortriptyline. Fluoxetine had exacerbated the symptoms. Clomipramine and fluvoxamine were partially effective but were associated with drowsiness. Current hormone replacement therapy included estropipate. Serum estradiol was 281 µg/1 and progesterone was 0.20 µg/1. T he patient was diagnosed as having obsessive compulsive disorder, anxiety and mild agitated depression coincidental with perimenopause. The symptoms improved with treatment with progesterone 100 mg p.o. t.i.d. on calendar days 1-15 and resolved completely with 200 mg three times a day. Hamilton Depression Rating Scale score improved from 18 to 11, and the Yale-Brown obsessive-compulsive questionnaire score improved from 20/40 to 5/40. Progesterone level rose to 29 µg/1 (serum estradiol of 275 µg/1) and serum estradiol/ progesterone ratio dropped from 1.402 pretreatment to 0.009. The patient has remained well for 3 years.

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