Assessing mood disorders that arise from POI is not always clear-cut. Emotional adjustment reactions to medical conditions as well as other diagnoses that contribute to ovarian dysfunction such as hypothyroidism produce similar symptoms. As with other mood disorders related to reproductive function such as premenstrual disorders and postpartum depression, some women have more pronounced mood responses to hormonal changes than others. This variation in patient response makes it easy for the clinician to overlook mood dysregulation related to POI. The most common mood disorders observed in POI patients are various forms of anxiety and depression . Within these categories are major and minor depression, dysphoria, obsessive-compulsive disorder, post-traumatic stress disorder, and social phobia [1].

Understandably, the reaction to receiving a diagnosis of POI while trying to conceive could precipitate a depressive episode. However, mood dysregulation has been shown to be present in POI patients when women are not trying to conceive [2]. Significant mood fluctuations may be symptomatic even before reproductive changes are detected. Some women, especially those with slower, earlier onset, may not notice emotional shifts as follicle-stimulating hormone (FSH) levels gradually increase, while others, especially those with POI due to surgical onset, may feel plunged into a deep abyss of unshakable dysphoria.

When a patient is unaware of POI due to the slow progression of FSH levels, or is not planning to conceive, the symptoms related to mood may be present. At a subclinical level, these symptoms may subtly impact the daily quality of life but not create an overall inability to function within social situations or at work to the degree that is required to receive a psychiatric diagnostic code. Energy levels may be lower; enthusiasm for previously enjoyed activities may be less, but these changes are easy to rationalize for women with busy lives that require multitasking and have constant distractions. Like the menopausal transition that occurs in older women, most POI is a process that occurs over a number of years [3]. Symptoms may be masked by years of oral contraception use which keeps amenorrhea and hypoestrogenic symptoms at bay until hormonal contraception is discontinued.

Retrospectively, POI patients often remember details that seemed unusual to them at the time. Some have reported that their hair began graying sooner than that of their peers, or they noticed skin changes such as age spots, and vaginal dryness occurring before their peers. The common use of hair color may mask the symptom, but women are often acutely aware of their graying well ahead of their peers. Lubricants solve the problem of uncomfortable intercourse. Other early symptoms that didn’t make sense at the time include sleep difficulties, hot flashes, and memory issues that are typical menopausal symptoms. Patients will report that their doctors have dismissed these concerns as situationally based and told the patient “not to worry.” This leaves the patient feeling frustrated and isolated. It is not unusual for a patient to have consulted with several doctors before a diagnosis of POI with the attending explanation of their symptoms is made [3].

There is evidence that women with long-term depression undergo menopause at an earlier age than women who have never been depressed [4]. However, there is no evidence that depression directly causes POI. Unlike women with age-appropriate menopause, women with POI are unique in that their depressive symptoms do not seem to be limited to the time they transition through perimenopause [5]. Depressive symptoms may have been experienced well before there is a disruption to the menstrual cycle, perhaps because of underlying changes in the hormonal milieu [6]. In their survey of POI women in a non-clinic-based sample, Allshouse et al. found that 49 % of the women were using antidepressant medication before they were diagnosed with POI. This is significantly higher than the 16.2 % reported in a population-based norm of women. Davis et al. [7] found that women with POI had an increased prevalence of both depression and anxiety.

Depressive and anxiety disorders have an overlapping symptom base. Both impact daily life; both include difficulty concentrating, irritability, sleep disturbances, and disordered eating [1]. Symptoms of depression or dysthymic disorder are sadness, poor appetite or overeating, low energy, poor concentration, insomnia, feelings of hopelessness, and self-criticism [1]. The difference between depression and dysthymia is the chronicity and duration of the symptoms. Women experiencing dysthymia may have had the symptoms for so long that they don’t recognize them as abnormal. In addition to some of the above depressive symptoms, a diagnosis of anxiety may include restlessness, exaggerated worrying, and muscle tension.

In contrast, patients with surgical onset of POI are often quite articulate when describing the difference between how they feel after surgery compared to what they felt like prior to treatment that left them with depleted estrogen levels. Not all patients who have oophorectomies, such as BRCA1 and BRCA2 carriers doing it as a prophylactic measure, require ongoing treatment, and HRT will help those women maintain mood quality. For those who have had oophorectomies due to cancer, the psychological changes experienced during chemotherapy [8] have been well documented. The treatments themselves can cause memory loss, depression, lack of energy, and sexual dysfunction even in patients who are not being treated for reproductively related cancers. POI patients may describe decreased mental energy, a lack of enthusiasm for things they previously enjoyed, being in a “mental fog” [5], memory loss, and irritability. In this case the symptoms may be severe enough to meet the diagnostic criteria for depression . When patients try to discuss these emotional and cognitive shifts, the feedback they often receive is that the symptoms are normal for someone who has just had surgery or has undergone subsequent chemo- or radiation therapy. It is easier to ascribe these psychological changes to the medical condition and the need to adjust to life after treatment, rather than to lasting endocrinological variations. However, the endocrinological and reproductive link should not be overlooked posttreatment. Patients need to be assessed for mood disorders after cancer treatment is completed. Offering hormonal as well as emotional or psychiatric support when normal psychological function is diminished is an important component of restoring the quality of life. Fertility rates after chemotherapy or radiation therapy are highly dependent upon age [9]; patients are commonly told they will require donor eggs to conceive.

At its most extreme end of the emotional spectrum, sudden-onset POI, whether surgical or receiving an unexpected diagnosis of sterility, can precipitate post-traumatic stress disorder (PTSD) symptoms. PTSD is well known to be present in patients who have experienced myocardial infarctions [10] and advanced-stage breast cancer [11]. An anxiety disorder , PTSD needs to be distinguished from transient, reactive stress that is often observed in POI patients. Among the characteristic symptoms are physiological reactivity when exposed to cues that symbolize the trauma, a sense of a foreshortened future, efforts to avoid thoughts and activities that arouse thoughts of the trauma, difficulty concentrating, and a restricted range of affect [1]. In a world where motherhood is celebrated as a rite of passage into adulthood and babies are present in many aspects of life, avoidance of cues is almost impossible. For POI patients, loss of fertility can be a reproductive trauma and crisis of identity stemming from fear of a compromised future. Women most at risk for PTSD symptoms after receiving a diagnosis of POI are those who have a history of borderline personality, a long history of depression, a cancer diagnosis preceding POI, or are single but actively trying to partner with the distinct purpose of having children. For these patients the psychological issues can cause more distress than the endocrinological ones. Referral to a mental health professional familiar with reproductive issues is recommended. For patients with PTSD postsurgical POI, psychotherapy to address the PTSD is best done after the medical treatment is complete, when the patient can adequately process the emotional content. Collaborative treatment between the reproductive specialist and the mental health professional for hormonal support and psychotropic medications is in order. Most important is to take the distress of these patients seriously.