Susan (45 years of age, gravida 3, para 2) underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy because of severe dysmenorrhea and a long history of atypical squamous cells of undetermined significance on Papanicolaou tests. She was healthy, not taking medication, and had no known allergies. Her past surgical history included hemorrhoidectomy and dilatation and curettage. There was no record of psychiatric illness, alcohol abuse, or any other substance abuse. She was a smoker, consuming one pack of cigarettes per day for 20 years.
Following the hysterectomy, Susan's gynecologist prescribed conjugated estrogens (Premarin) 1.25 mg. Two weeks later, the dose was decreased to 0.625 mg to treat symptoms of right hand numbness and tingling. A week later, her prescription was switched to estradiol TD patch (Estraderm) 0.1 mg for her continuing symptoms of paresthesia and jitteriness. That same day, she presented to the emergency department (ED) complaining of shaking, shortness of breath, and headaches. She was diagnosed with anxiety disorder, treated with diazepam (Valium), and referred to the internal medicine department for further evaluation. Her following examinations and laboratory studies were all normal. The cycles repeated when she presented to the ED on subsequent visits with identical symptoms. She was again treated with diazepam, and follow-up was arranged with either the mental health or family practice department, depending on the provider treating her in the ED and the specialist she was seeing at the time. The mental health provider discontinued her estrogen replacement therapy (ERT) and prescribed diazepam, but her primary care provider put her back on the ERT. Her care was remarkably episodic, and the lack of communication between the providers proved problematic.
While symptoms tend to be similar, their onset is much more abrupt in surgical menopause than in natural menopause.
This patient first presented 11 months after her surgery to discuss the ERT. At the time, she was on estradiol TD patch but wanted to switch back to oral conjugated estrogens because the patch would not adhere sufficiently to her body. Based on her history, the nurse practitioner (NP) prescribed conjugated estrogens 0.625 mg daily. Five months later, she was in the ED again with anxiety symptoms and then at the mental health clinic where she was told to stop the ERT. She contacted her NP for guidance and the NP collaborated with the mental health provider. It was determined that Susan should continue with her ERT. Her estrogen dose was increased to 1.25 mg 3 months later when she continued to have menopausal symptoms such as hot flashes, sleep disturbances, and alterations in mood. She presented to the OB/GYN clinic 9 months later for her annual examination and reported that she was doing well and that she had been free of anxiety attacks for 1 year. Finally, her hormonal level reached the effective stage to counter symptoms of anxiety, and she had an overall feeling of well-being.
Surgical Menopause
Hysterectomy is the second most frequently performed major surgical procedure for women of reproductive age in the United States. Approximately 600,000 hysterectomies are performed annually, and an estimated 20 million U.S. women have under-gone hysterectomies. 1 Between 1994 and 1999, one in every nine women 35 to 45 years of age had a hysterectomy. Just over one-half also had a bilateral oophorectomy. 1 The most common primary diagnoses for a hysterectomy were uterine leiomyoma, endometriosis, and uterine prolapse. 2
The onset of surgical menopausal symptoms is abrupt and often dramatic with oophorectomy. The out-come of postsurgical changes is influenced by preexisting physiologic and psychological conditions, and its associated menopausal symptoms can have a significant impact on quality of life.
Etiology
The natural transition from the reproductive years to postmenopause represents a lengthy continuum of biologic changes. Much diversity exists among individuals in terms of the menopausal symptoms that often accompany these changes. Surgical menopause, however, does differ from natural menopause in its impact and effects. While symptoms tend to be similar, their onset is much more abrupt in surgical menopause than with natural menopause. 3 The physical and psychological changes that extend from this precipitous drop in endogenous estrogens and androgens tend to be more dramatic and generally have a significant impact on a woman's quality of life. Although disturbances in mood and behavior may not occur uniformly with menopause, an excess of somatic, mood, and behavioral symptoms are associated with both surgically induced and natural menopause. 4 Furthermore, many postmenopausal women describing their experiences of mood changes, such as depression, irritability, or aggressiveness, suggest ovarian hormones play a role in psychological health. 5 Reports of anxiety attacks generated by surgical menopause that require immediate medical attention are lacking in the literature, however.
Leading menopause-related complaints in order of frequency are as follows: hot flashes, night sweats or chills, disrupted sleep, vaginal dryness, loss of libido, loss of energy, mood swings, increased irritability, loss of skin tone, and urinary leakage. Vaginal dryness was reported by approximately 20% of women, and loss of libido was reported by 15%. A study of surgically menopausal women generated a similar listing: fatigue, short-term memory deficits, hot flashes, and sleep disturbances. 6
The outcomes of surgical menopause are individually influenced by physical, psychological, and social issues. Preexisting illness, psychiatric disorder, or social dysfunction can profoundly affect the perception of risk and the expression of postoperative events. In women who manifest problems prior to menopause, whether physical or emotional, there tends to be an exacerbation after menopause, particularly with disorders of sexual desire, sexual response, and sexual behavior. 7
The timing of surgical menopause is likely to have an effect on emotional condition. Pinhey and Pinhey 8 examined the emotional consequences of the time of surgical menopause. Their study supported the hypothesis that off-scheduled life events result in considerable emotional trauma. In Guam, women 44 years of age or younger were significantly more likely than women over the age of 44 to suffer psychological distress after experiencing surgical menopause. Psychological distress after hysterectomy may be the result of deviation from age-norms rather than an outcome of the physiological loss of estrogen. Thus, it can be interpreted that emotional consequences are dependent on a woman's perception of the appropriate timing for life events.
In a prospective study, Khastgir, et al 9 found the incidence of depression was higher before hysterectomy in women with preexisting psychiatric illness, and that depression resulted from the emotional response to gynecologic symptoms or a manifestation of associated ovarian failure. This report suggests that hysterectomy may not be directly related to the cause of postoperative psychological complaints; rather, it may be a general complaint of preexisting symptoms. Kjerulff et al 10 supported this conclusion. The risk of a poor outcome after hysterectomy increases among women who are in therapy for emotional problems at the time of hysterectomy.
Pathophysiology
Ovarian hormone biosynthesis plays an important role in the production of estrogens and androgens, derived from both the ovaries and adrenal precursors. The pituitary gland secretes follicle-stimulating hormone (FSH), which stimulates the aromatase enzyme system to convert androgens into estrone (E1) and estradiol (E2). Testosterone and androstenedione of both adrenal and ovarian origin are also substrates for estrogen formation in peripheral tissues. Additionally, pituitary luteinizing hormone stimulates ovarian production of androstenedione and testosterone from cholesterol. Stimulated by FSH, they are then converted into E1 and E2. After menopause, the primary estrogen produced is E1, derived principally from peripheral aromatization of adrenal androstenedione. 11 The low circulating levels of estrogen in the naturally post-menopausal woman result in menopausal symptoms. In surgically menopausal women for whom supplemental estrogen is prescribed, however, sex hormone-binding globulin (SHBG) levels increase dramatically, resulting in reduced bioavailability of the remaining estrogens and androgens that derive from peripheral conversion.
The relationship between estrogens, androgens, and SHBG represents another dimension of the hormonal milieu and is important for the clinician. Sex hormone-binding globulin regulates the proportion of total hormone available for action and/or metabolism at target sites in the periphery. 12 Androgens bind to SHBG; therefore, high levels of SHBG reduce the levels of these hormones available to target tissues. High levels of estrogen are associated with elevated levels of SHBG. A menopausal woman who is prescribed supplemental estrogen may experience an increase in SHBG and a resultant decrease in bioavailability of both endogenous androgens and estrogens as SHBG also binds (but with less affinity) to estrogens. The resulting hormonal deficiency is an issue that potentially affects all menopausal women; it is of particular significance for surgically menopausal women who are already deprived of the ovarian hormone production that continues after menopause.
Physiologic Changes and Symptoms
After menopause, women obtain most of their circulating estrogen from the peripheral aromatization of adrenal and ovarian androgens. The ovaries of menopausal women continue to be important sources of androgen production, as demonstrated by comparison with women who have had oophorectomy and experience a dramatic decline in circulating androgens. 11 Compared with several years for natural menopause, bilateral oophorectomy has shown a dramatic drop in circulating estrogens and testosterone levels (<10 pg/mL and 5 ng/dL, respectively) within 24 to 48 hours after surgery. 13,14 Associated with these abrupt and significantly reduced hormonal levels, menopausal symptoms in surgically menopausal women are generally much more severe than those associated with natural menopause. 3
Although prevalence and severity of symptoms differ significantly, the sudden decrease in ovarian hormones commonly results in dramatic symptoms, predominately vasomotor instability (e.g., hot flashes, increased perspiration, night sweats, and insomnia), decreased libido, and a lessened feeling of general well-being. 7 Furthermore, more women who had surgical menopause reported climacteric symptoms and more severely intensive vasomotor instability than women experiencing natural menopause. Fatigue, short-term memory deficits, and sexual function, including urogenital atrophic changes, are also identified as problematic areas. 6 Sexual dysfunction after menopause or hysterectomy has been classically attributed solely to the loss of functional estrogen. Symptoms of urogenital atrophy are clearly estrogen mediated: vaginal dryness, dyspareunia, discharge from atrophic vaginitis, dysuria, and other irritating symptoms. 15
Psychological Changes and Symptoms
Psychological changes during menopause are accompanied by symptoms resulting from hormonal changes, which may significantly affect a woman's sense of well-being. For example, direct urogenital and sexual implications related to loss of ovarian function affect sex drive, sexual response, vaginal dryness and dyspareunia, dysuria, and urinary urgency, which affects a woman's sexual relationships and psychological condition. Because prevalence and severity of surgical menopausal symptoms are also associated with preexisting psychological and physical problems, symptoms will vary among women. For women with menstrual disorders or complicated reproductive histories, menopause may bring a newfound freedom and comfort regarding sexuality, whereas women with unstable psychiatric conditions may experience postsurgical exacerbation of those problems. 7
Ryan et al 16 evaluated 60 women 30 to 55 years of age who had hysterectomies for benign conditions. Women considered well-adjusted suffered no adverse psychological distress; however, those with underlying disorders had problems. Principal risk factors of poor psychological outcome were high baseline scores on presurgical mental health measures and personality inventory or past psychiatric treatment. Depression may persist or arise for the first time with the loss of ovarian hormonal support in some patients with preexisting mood disorders. 9 Pearlstein et al 17 related that women seeking treatment for menopausal symptoms are more likely to have a previously undiagnosed affective disorder. Moreover, Ishimaru-Tseng 18 reported that many women distressed by menopausal symptoms are manifesting an underlying previously undiagnosed bipolar affective disorder.
Differential Diagnosis
Regardless of age or reproductive status, women experience mood disorders more often than men; the lifetime risk for a major depressive episode ranges from 10% to 26% in women versus 5% to 12% in men. 7 The prevalence rates appear to be unrelated to ethnicity, education, income, or marital status. Women also are two to three times more likely to develop dysthymic disorder than men. This condition is characterized by two or more of the following symptoms: poor appetite or overeating, insomnia or hypersomnia, low energy or fatigue, low self-esteem, and poor concentration or difficulty making decisions, and feelings of hopelessness. 19 Bipolar disorder is equally common in women and men. Late-onset bipolar illness may be associated with stressful life events, such as menopause. Certain symptoms commonly ascribed to menopause (e.g., irritability, fatigue, and sleeping difficulty), may be complicated or made worse by an underlying bipolar disorder. 18
Psychological changes during menopause are accompanied by symptoms resulting from hormonal changes.
When depressed, women more often describe somatic symptoms and weight gain (rather than weight loss). Common menopausal symptoms may resemble those of depression, making it difficult to distinguish between the conditions. Late-life depression among the elderly-the most common mood disorder at this stage of life-may further complicate the differential diagnosis of mood changes in this age group. 20
Minor mood disorders often go unrecognized and therefore untreated. Women attending gynecologic clinics are more likely to exhibit somatization, borderline personality, or cyclothymic disorder than full-blown depression. Many times, they repeatedly present with chronic conditions such as undiagnosed chronic pelvic pain, unconfirmed vulvovaginitis, vulvodynia, or dyspareunia. A simple scale such as the Beck Depression Inventory may prove helpful for identifying women suspected of undiagnosed depression. 7
Diagnosis
Because of the coincidence in time and exclusion of other possible etiologic factors (e.g., primary psychiatric disorder, exacerbation of preexisting psychiatric illness, or personality and psychosocial problems), Susan's (case report) severe acute anxiety attacks were most likely a response to the physiological loss of estrogen from surgically induced menopause. Since menopause has previously been reported to cause psychological symptoms, this ovarian failure must be the first suspect. The patient had no pre-existing psychiatric illness preoperatively, nor did she express negative emotional perceptions of fertility loss through early surgical menopause.
Treatment
One of the key factors affecting a patient's decision to begin hormone replacement therapy (HRT) is the impact that menopause has had on her physiologic and psychological balance in the day-to-day management of life issues. In the case of the surgically menopausal woman, the relative contributions of estrogen and androgen to the maintenance of that balance can be explained by describing the positive and negative effects of the therapy. More importantly, the counseling process should be done before the surgery to include discussions of the procedure, the resulting physiological and psychological changes, and the therapeutic options.
Numerous studies have demonstrated the effect of estrogen and estrogen/androgen therapy on libido and mood in postmenopausal women; in these studies, treatment most often took the form of oral conjugated equine estrogen (0.625 or 1.25 mg) and methyltestosterone (2.5 mg/day) taken for up to 24 months. The average patient on HRT had 76% lower levels of depressed mood than untreated women. Estrogen alone significantly countered depressive feelings 21 and enhanced mood and cognitive performance. 22
Androgen therapy, however, was the most effective option, whether given alone or in combination with estrogen in reducing distress, anxiety, and depression after 2 months in women with menopausal symptoms. 21 Sherwin 23 also reported that estrogen alone or combined with testosterone had positive mood changes in surgically menopausal women. However, women on the combined regimen felt more composed and energetic than those given estrogen alone, and their depression scores declined more rapidly. In addition, estrogen-androgen therapy correlated with less anxiety and hostility and with increased positive feelings when compared with control subjects. A study by Gelfand 1 also supports the results of other reports in that estrogen-androgen replacement therapy significantly improves energy levels and an overall sense of well being among surgically menopausal women with respect to estrogen alone. In addition, this combined therapy significantly enhanced sexual desire, sexual arousal, and frequencies of coitus and orgasm.
The acute onset of surgical menopause is of primary concern for patients who undergo hysterectomy with bilateral oophorectomy. Thus, to eliminate most symptoms associated with surgical menopause, initiation of HRT, estrogen alone, or estrogen-androgen should be considered for these women. This treatment recommendation is based on the provision that the diagnosis is not cancer of the uterus and there are no other serious contraindications to HRT.
Counseling, plus the appropriate hormonal support, can improve psychological functioning and quality of life.
REFERENCES