Diagnosis

Physical exam showed normal vital signs and a BMI of 27.5. There were no abnormalities in skin texture or hair thinning. Examination of the thyroid revealed no enlargement, nodularity, or tenderness. Pelvic exam revealed normal external female genitalia, mild vaginal mucosa atrophy, and an atrophic appearing cervix. There was no cervical motion tenderness, adnexal tenderness, or adnexal masses on bimanual exam. With laboratory results and imaging studies ruling out any other possible etiologies, a diagnosis of vasomotor symptoms associated with menopause was established.

Management

The treatment of vasomotor symptoms of menopause is recommended when symptoms are present and bothersome. For women with mild hot ushes that do not interfere with daily activity, treatment is not indicated. When symptoms become moderate (interfere somewhat with daily activity) or severe (daily activities cannot be performed), treatment is recommended. Associated symptoms such as sleep disturbances and mood changes should be assessed because the recommended therapy should target the symptoms which are most bothersome to the patient.

Behavioral changes should always be discussed with the patient frst. This primarily includes dressing in layers which can be removed or added, using a fan or lowering the ambient temperature when possible, avoiding hot ush triggers (tobacco, spicy foods, and painful stimuli), and weight loss for overweight patients.

For patients with moderate or severe vasomotor symptoms, hormone therapy is recommended for women without contraindications [1]. Hormone therapy is generally safe for healthy women who are less than 10 years from the menopause or less than 60 years of age and do not have undiagnosed vaginal bleeding, a history of breast cancer, untreated endometrial cancer, cardiovascular disease, prior deep vein thrombosis, or active liver disease. Risk of developing cardiovascular disease and breast cancer should be assessed and hormone therapy should be avoided for patients that are considered high risk.

Once a patient decides to initiate hormone therapy, a strategy of using the lowest effective dose for the shortest time needed should be utilized. This can be done by starting at a low or moderate dose and titrating up or down as needed until symptom control is achieved. After a few years of treatment, attempts to wean the patient off of hormone therapy should be made every 1–2 years. This will help to minimize the risks associated with long-term hormone therapy use. Women without a uterus should be treated with estrogen therapy alone. Women with a uterus must be treated with estrogen and a progestin to oppose the effects of estrogen on the endometrium.

Common routes of estrogen therapy include oral, vaginal [2], and transdermal patch or gel. Progestin therapy is most often administered as oral micronized

A special population to consider is women with breast cancer. Hormone therapy is contraindicated for this population and therefore nonhormonal options should be used. For women currently taking Tamoxifen for endocrine therapy of disease, certain SSRIs should be avoided. Tamoxifen is converted to its active metabolite, endoxifen, by CYP2D6. Paroxetine and Fluoxetine are strong inhibitors of CYP2D6 and theoretically could decrease the effcacy of tamoxifen therapy. While no evidence that taking these SSRIs concomitantly with tamoxifen increases breast cancer recurrence, it is generally best to avoid these two medications for patients taking tamoxifen. Other SSRI/SNRIs or gabapentin are acceptable alternatives.

This patient was deemed a good candidate for hormone therapy due to being both less than 60 years old and shorter than 10 years away from the menopause. She does not have any contraindications and her 5-year risk of developing breast cancer was calculated to be 2.4%. She was treated with initiation of transdermal estradiol 0.025 mg weekly and oral micronized progestin 200 mg/day for the frst 12 days each month. After 1 month, she reported her daytime hot ushes had improved signifcantly, but that she continued to have night sweats and sleep interruptions. She was then initiated on gabapentin 100 mg nightly. After 4 weeks, she reported improvement in symptoms, now only waking from sleep with night sweats 2–3×/ week. Her daytime drowsiness is now resolved and her focus at work is greatly improved. She also reported her motivation to exercise has increased and she is now back at the gym 3×/week, which she attributes to her improved sleep and decreased irritability throughout the day.

Discussion

The average age of menopause in the USA is 51. As the ovarian follicular pool decreases in the years leading up to menopause, there are less granulosa cells present in the ovary. These cells are responsible for secreting many of the regulators of the hypothalamic-pituitary axis including inhibin-B, inhibin-A, activin, anti-­Mullerian hormone (AMH), and estradiol. AMH and inhibin-B regulate follicle stimulating hormone (FSH) secretion and the follicular response to this hormone. As AMH and Inhibin-B levels gradually decrease with the declining follicular pool, FSH levels prematurely rise to stimulate follicular growth and a resulting rise in estradiol levels. In the last 1–2 years before the menopause, a major decline in estradiol occurs until they plateau shortly after the menopause in a range between 10 and 20 pg/mL.

It is in response to the decreased circulating estrogen levels that menopausal symptoms arise. These symptoms are partially explained by a change in the thermoregulatory zone which can occur in response to decreased estrogen levels in women around the time of menopause. This change in estrogen levels can lead to altered regulation of central neurotransmitters resulting in a narrowed thermoregulatory zone in which sweating is triggered at a lower temperature. However, approximately 25% of women do not experience hot ushes after the menopause and therefore decreased estrogen levels alone do not fully account for vasomotor symptoms experienced by most women [9].

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