© Springer International Publishing Switzerland 2016
Nanette F. Santoro and Amber R. Cooper (eds.)Primary Ovarian Insufficiency10.1007/978-3-319-22491-6_33. Signs and Symptoms of Primary Ovarian Insufficiency
(1)
Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO 80045, USA
(2)
12477 E 19th Avenue, Building 406, Room 109, Aurora, CO 80045, USA
(3)
International Premature Ovarian Failure Association, Inc. (IPOFA), Alexandria, VA, USA
Keywords
Premature menopausePremature ovarian failurePremature ovarian insufficiencyPrimary ovarian insufficiencyInternet surveyInfertilityPOFPOIEarly menopauseVignettes
1.Before I was diagnosed with POF, I would have hot flashes—I remember them as early as 21, sitting in my college class. I really didn’t think anything of it. Throughout my early 20s, I would have ovarian cysts “rupture,” which were very painful, and at times, I would faint from the pain. I was diagnosed with endometriosis and had several surgeries. When I was in my late 20s, I went to a fertility doctor because I could not get pregnant. My FSH level was over 100, and I was told there would be no way for me to have my own children. I felt like an old woman. I decided that I would not let this defeat me. I lost 70 lbs. by running, lifting weights, and eating healthy. I thought that by doing this I would restore my fertility; however, I was wrong. Eventually, I used donor eggs and had my daughter this past October. Actually, finding out that I had POF made me reevaluate my life and realize that there are things I can control and things I cannot. I don’t believe I would have ever lost the weight or starting running if I didn’t find out I had POF, so as strange as it may sound, I am thankful for it.—Rachel, age 35 (6 years since diagnosis)2.Prior to my POI diagnosis, my symptoms were both physical and emotional. My periods were never regular. I started to have issues with an anxiety disorder at 19. At 27, I was diagnosed with hypoglycemia. In my mid-thirties I was diagnosed with low blood pressure, and night sweats and hot flashes began when I was 34. Coinciding with the vasomotor symptoms were mental fog, increased attention deficit disorder, clicking and clunking in my hip joints, muscle tightness throughout my body, and exhaustion. I was in therapy for most of my twenties to deal with the anxiety disorder, which was quite helpful. I am an avid gym-goer, which kept me physically and mentally strong throughout. I keep a strict diet of high protein and carbs to balance the hypoglycemia, and I drink way too much coffee to counteract the low blood pressure.I was diagnosed with POI at 36. At that time, I started hormone replacement therapy. I take 1 mg/day estrogen, 2.5 mg/day progesterone, and 2 drops/day testosterone. With HT, the night sweats, hot flashes, and exhaustion went away; however, the clicking and clunking in my hip joints and the muscle tightness throughout body persist; mental fog has decreased, ADD is back to my “normal,” hypoglycemia diminished, and the anxiety disorder greatly lessened.It was a great challenge to be told not only that I was in menopause in my mid-thirties, making me feel much older than I actually was, but to make matters worse, told “…you will never have your own children.” As I had yet to start a family, it was quite devastating to hear this. I did not find much sympathy from friends or family and now still find odd reactions from people when they find out I don’t have children. Sometimes, I tell them I can’t, while other times I just let them go ahead and judge me almost as if asking “what kind of woman doesn’t want children?” Being involved with POI support organizations and doing what I can to help the cause for POI make me feel that at least I can see that some good comes from this diagnosis. Being fit and active has been a huge benefit to me throughout. Now, I’m old enough to pretend I’ve raised my kids and am living the life people lead when this happens.Pre-POI was awful, the process of diagnosis of POI was horrendous, but now the post POI…not so terrible, all things considered.—Amy
Introduction
The symptoms of age-appropriate menopause are well documented [1] and appear to diminish appreciably within several years of the final menses [2]. Women with POF/POI often exhibit evidence of sporadic ovarian function and pregnancy, sometimes long after the diagnosis is established [3]. The nature and length of additional symptoms specific to POF/POI are less widely understood. POF/POI is associated with anxiety, depression, stress, irritability, nervousness, decreased libido, lack of concentration, hot flushes, weight gain, dry skin, vaginal dryness, and increased autoimmunity disruption [4–6]. A prospective, longitudinal cohort of women studied both before and after a POF/POI diagnosis, with comparison groups of age-similar women without POF/POI and women traversing age-appropriate menopause, would be the gold standard method of tracking and attributing symptoms of POF/POI; however, such a cohort would be difficult to construct because of the low prevalence of POF/POI and the difficulty in identifying women who are at greater risk, making a retrospective study design more feasible [7]. Asking women to recall symptoms that occurred in the past could potentially be an unreliable method of collecting data, due to the known difficulties of recall bias. Comparing current symptoms across women with varying numbers of years since POF/POI diagnosis allows for a comparison of the nature of differences in POF/POI symptom prevalence over time since diagnosis between women.
The body of this chapter references our cohort, where 160 women diagnosed with POF on average 10 years before taking the survey were asked about current symptoms [8]. In our cohort, respondents were recruited through an online support group facilitated by The International Premature Ovarian Failure Association (IPOFA) organization and asked to complete an online anonymous survey designed to further illuminate the symptoms associated with POF/POI. In addition to the inclusion of validated instruments [9, 10] and additional specific symptoms, multiple opportunities to write-in responses were offered. Responses from many of such write-in opportunities are included in this chapter. Symptom prevalence generally did not greatly decline with time since diagnosis.
The consequence of infertility is perceived differently by women diagnosed with POF/POI, depending on whether their family planning goals had been achieved prior to diagnosis. For some, the difficulty of infertility outweighs any independent physical or mental symptoms and could be a source of additional anxiety or depression. Mood, symptom, and fertility questions specific for women with POF/POI could better articulate the burden brought on by this diagnosis.
Diagnosis
While a POF/POI diagnosis in a woman under age 30 is rare (0.1 %), case reports featuring these diagnoses share a similar trend, that the change in menstruation from regular to irregular cycles [11, 12] prompts the diagnosis. In general, women who experience early amenorrhea due to POF/POI do not report prodromal symptoms [13]. As the diagnostic process can involve ruling out other conditions and running multiple tests [14], a POF/POI diagnosis can take time and input from a team of providers.
Among women in our cohort, the number of types of providers seen for treatment and/or management of POF/POI exceeded 9 for some, with half of women requiring four or more health-care providers. A gynecologist was seen most commonly for POF/POI (89 %), followed by a reproductive endocrinologist (79 %). Alternative medicine was utilized by several women as indicated by 34 % who visited an acupuncturist, 17 % who frequented massage therapists, and 11 % who visited a chiropractor. The duration of time between the onset of symptoms and the diagnosis of POF/POI was not associated with a different number of providers seen for treatment.
Management of Symptoms
Although some menopausal symptoms have been found to persist or worsen over time, many women in our cohort reported feeling that they had adequate management of symptoms. Women who were diagnosed more recently reported a lower rate of satisfactory symptom management (60 %) than women diagnosed more than 5 years ago (75 %). When asked how long before symptoms were adequately managed, 50–75 % of women were able to control symptoms within 0.5–2 years. Even though 27 years after a diagnosis, one woman reported that her symptoms were not adequately managed, the overwhelming majority of women diagnosed 10 years or more felt symptoms were adequately managed. Women taking hormonal therapy reported having achieved symptom management at a greater rate (71 % for 1 hormone, 81 % for 2 hormones, 83 % for 3 hormones) than those reporting no HT usage (47 % reported satisfactory symptom management). When symptoms persist over time, the right combination of treatments to manage symptoms is attainable for many.
Menopause-Like Symptoms
Age-appropriate menopause occurs between ages 45–54, with a median age of 51.4 at the final menses [16]. Age-appropriate menopause is often accompanied by hot flashes, night sweats, sleep problems, mood changes, and vaginal dryness [1]. POF/POI is also associated with these symptoms. POF/POI occurs earlier in life and is more likely to be marked by a return of menses, ovulation, and possibly pregnancy [17–21]. In contrast with age-appropriate menopause, women with POF/POI have frequent evidence of sporadic ovarian function and pregnancy, sometimes long after the diagnosis is established [3]. This can lead to both unexpected hormonal fluctuations, a lingering hope for a treatment-free resolution to fertility challenges, and also to repeated episodes of hormonal withdrawal when ovarian function stops. While age-appropriate menopause is traversed by an age cohort together, increased isolation from peers in managing the symptoms and consequences is reported by women with a POF/POI diagnosis.
The Menopause-Specific Quality of Life Questionnaire (MENQOL) is a validated instrument used to assess health-related quality of life in the postmenopausal period and consists of 29 Likert-scale formatted items. Each item assesses the impact of one of four domains of menopausal symptoms, as experienced over the last month in the following order: vasomotor (3), psychosocial (7), physical (16), and sexual (3). Items pertaining to a specific symptom are rated as not present (score = 1) or present (score = 2) and if present, how bothersome on a zero (not bothersome) to six (extremely bothersome) scale. The resulting total score on any one item ranges from one to eight. Means are computed for each subscale by dividing the sum of the domain item scores by the number of items within that domain. A higher score indicates poorer quality of life.
From MENQOL responses in our cohort, 46 % of women reported currently experiencing hot flushes, 40 % experience night sweats, and 34 % reported sweating (43 % of whom were bothered to some degree by sweating). Additional write-in responses from our cohort along the line of vasomotor symptoms included attributing the following symptoms to POF/POI: body odor from sweat and heat intolerance.
In our cohort, time since diagnosis in years was weakly negatively correlated with the MENQOL vasomotor domain indicating that, with time, these symptoms did not improve and in fact worsened. Comparing women who were diagnosed within the past 5 years to women who were diagnosed longer ago, more recently diagnosed women had a higher menopause-related quality of life for both vasomotor and psychosocial symptoms. These results indicate that with time and age, symptoms of POF/POI may persist and/or increase, in contrast with the experience of age-appropriate menopause [16].
Weight and GI Symptoms
As age-appropriate menopause occurs in tandem with the aging process, it is also associated with weight gain, slowed metabolism, and increased cardiovascular risk—related primarily to the aging process. An increase in trunk and leg fat with POF/POI among women undergoing chemotherapy for breast cancer [22] and increased risk of weight gain among premenopausal women undergoing hysterectomy, even without bilateral oophorectomy [23], have demonstrated increases in weight among women undergoing surgical processes similar to primary POF/POI.
Several women in our cohort reported turning to exercise to manage symptoms, which is reflected in the distribution of current weight in our cohort, with 56 % in the normal BMI category. Pre-obesity (BMI 25–<30) was the current state of 25 % of our cohort, and obesity was observed in classes I (9 %), II (3 %), or III (3 %), with the remaining 4 % being underweight. When asked for a target weight, 85 % of women successfully identified a weight that would place their BMI in the normal range. From the MENQOL, 46 % of our cohort reported weight gain in the past month, and 50 % report feeling bloated.
Women in our cohort reported attributing weight-related symptoms to POF/POI: irregular appetite, increase in appetite, difficulty losing weight, weight gain, midsection weight gain, increased breast size, and weight changes. Some women reported symptoms of weight loss, in some cases concurrent with a decrease in breast size. Additionally some women in our cohort report experiencing symptoms related to digestion: abdominal bloating, gastrointestinal issues, and constipation. Additional research would help better document these symptoms on a wider scale in this population. From the MENQOL, 50 % of our cohort reported flatulence or gas pains in the past month.
Mindfulness and Mental Fog
Women who have undergone surgical menopause including oophorectomy may have short-term poorer cognitive function [24]. Nearly half of the women (48 %) in our cohort reported “mental fog” in the past 30 days, 69 % of whom found the mental fog to be moderate or severe. From the MENQOL, 69 % reported experiencing poor memory. Additionally, other variations of cognitive impairment were provided in a write-in opportunity: brain fog, aphasia, difficulty concentrating, forgetfulness, memory issues/loss, and losing train of thought.
Using a validated instrument, the Cognitive and Affective Mindfulness Scale-Revised (CAMS-R) [10] to assess mindfulness of thoughts and feelings, we further assessed attention, present-moment focus, awareness, and acceptance/nonjudgment in our cohort. Each CAMS-R domain score and time since POF/POI diagnosis were shown to be poorly correlated, indicating that there is little difference in mindfulness between women diagnosed recently and women diagnosed more than 20 years ago. This suggests that similarly to women who undergo surgical menopause, women with POF/POI could suffer cognitively and these symptoms could persist over time.
A synergistic effect of physical symptoms and mindfulness is plausible. Women who experienced more severe symptoms demonstrated lower levels of mindfulness as measured by the CAMS-R in each domain and overall.
Additionally, women reporting mental fog in the past 30 days reported lower levels of mindfulness than women not reporting mental fog. Increased physical symptoms and mental fogginess can decrease a woman’s mindfulness. This constellation of symptoms can be difficult to articulate for patients, in part because of the feeling of fogginess and in part because of the lack of specificity of the term. Attentiveness to the need to ask probing questions regarding symptoms of mindfulness and mental fog could improve patient/clinician communication.
Depression
A history of depression is highly prevalent among women with POF/POI, as demonstrated by our cohort where 43 % of women reported a history including a diagnosis of depression and a previous work [25] where 67 % of women with POF/POI had a lifetime history of either major (55 %) or minor (13 %) depression. Among women with a history of a diagnosis of depression, the diagnosis of depression preceded the POF/POI diagnosis for many, 43 % [8] and 68 % [25]. For the 43 % of women in our cohort with depression for whom the depression came first, it was diagnosed within 5 years prior to POF/POI for 40 % and more than 5 years before POF/POI for 60 %. From MENQOL responses in our cohort, 51 % reported feeling depressed in the past month, and 50 % reported feeling dissatisfied with their personal life in the past month. The association between POF/POI and depression has been suggested to be overlapping pathophysiology [25] or bidirectional in our cohort, as opposed to causal.
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