1. c. The most likely diagnosis in this patient is menopause. Menopause is a retrospective diagnosis based on 12 or more months of amenorrhea occurring at a mean age of 51   years. The diagnosis is based on the appropriate age of a female patient for menopause (range, 45 to 55   years), symptoms of frequent classic “hot flashes,” night sweats, and the association of these symptoms with the cessation of menses. Although the patient does have some symptoms associated with the other conditions listed, her lack of other complaints (hair loss, diarrhea, and palpitations) or previous history of an affective disorder (depression, anxiety, and panic) along with her normal vital signs and essentially normal physical examination makes the diagnosis of these other conditions less likely. The findings of vulvovaginal atrophy are also consistent with menopause.

2. b. The most effective treatment for this patient’s vasomotor symptoms is HT (estrogen combined with a daily or cyclic progestin/progesterone). A progestin or progesterone alone may alleviate some of this patient’s symptoms, but her symptoms are related primarily to estrogen deficiency and thus respond best to ET. However, this patient still has her uterus, and ET (estrogen alone) is not recommended because of the significantly increased risk of endometrial hyperplasia or cancer with prolonged unopposed estrogen use. Antidepressants might help alleviate some of this patient’s symptoms, especially if she was also clinically depressed. However, this patient’s symptoms are most likely hormonally related, and HT/ET alone often alleviates both the affective and the somatic symptoms of menopause. There is no strong evidence that this patient has hypothyroidism, and there is certainly no indication for empirical use of thyroid hormone without objective evidence of hypothyroidism (i.e., thyroid-stimulating hormone and thyroid function test).

3. d. Although ET/HT remains the most effective therapy for this patient’s vasomotor symptoms, many women will not or cannot use estrogen. All of the therapies listed have been evaluated for effectiveness in alleviating hot flushes and night sweats associated with menopause. Data for these therapies are limited, and most of the studies have been conducted on women with a history of breast cancer. Various SSRIs and particularly the SSNRI venlafaxine have been shown to reduce hot flushes 19% to 60% and were well tolerated by study participants. Small studies evaluating gabapentin have also demonstrated significant reductions in vasomotor symptoms. Clonidine patches have demonstrated some efficacy in reducing vasomotor symptoms, but dry mouth, constipation, drowsiness, and application site irritation are potential side effects. Soy isoflavones reduced hot flushes in some trials, but most trials showed no difference compared with placebo. Black cohosh and red clover have also had inconsistent results, with some trials showing benefit and some no difference compared with placebo. Other agents that have been used to alleviate hot flushes include belladonna/ergotamine tartrate/phenobarbital combination, dong quai, evening primrose oil, ginseng, mirtazapine, trazodone, vitamin E, and wild yam, but few data regarding their effectiveness have been published.

4. e. Symptoms of urogenital atrophy related to menopause (estrogen deficiency) include vaginal dryness, vaginitis, dyspareunia, dysuria, urinary incontinence, and recurrent UTIs. Intravaginal estrogen creams or tablets (usually inserted daily initially and then two or three times per week) and the estrogen-embedded vaginal ring, Estring (changed every 3   months), are highly effective for reducing both the signs and the symptoms of urogenital atrophy, with significantly less systemic estrogen absorption compared with oral or transdermal ET. Although the risk of venous thromboembolic events is minimized, there is no strong evidence that they are less likely to increase the risk of other cardiovascular events (i.e., myocardial infarction and cerebrovascular accident) or breast cancer. Vaginal moisturizers and increased vaginal sexual activity also help with vaginal lubrication and reduce atrophic symptoms.

5. a. The WHI was the largest multicenter clinical investigation of postmenopausal women, having recruited more than 60,000 patients. The WHI included a randomized, double-blind, placebo-controlled set of three trials and one observational study to examine the effects of various interventions on the major causes of morbidity and mortality in postmenopausal women, namely, CHD, breast cancer, colon cancer, and osteoporotic fractures. One arm of the WHI observed 16,608 healthy patients aged 50 to 79   years at baseline, with an intact uterus, taking either HT (0.625   mg of CEE combined with 2.5   mg of MPA) or placebo. On July 9, 2002, 5.2   years after study initiation (intended duration, 8   years), the HT portion of the trial was halted because of the findings that the overall health risks of treatment (observed increases in CHD, venous thromboembolism, and breast cancer) outweighed its benefits, which were observed decreases in osteoporotic fractures and colon cancer (Fig. 74-1 and Table 74-1). However, these increases in adverse events in the treatment group were small, and there were no significant differences between groups regarding endometrial cancer and mortality from any causes.

6. e. The HT arm of the WHI randomized controlled trial (RCT) did demonstrate a higher relative risk of cardiovascular events (myocardial infarction, cerebrovascular accident, and venous thromboembolism) and breast cancer compared with the control group. However, the absolute risk of these events attributable to HT is small, and no cause-and-effect conclusions should be inferred. In addition, these findings may not apply to other estrogen and progestin formulations, combinations, dosages, and routes of administration (i.e., transdermal and intravaginal). However, it is reasonable to infer from these data that the combination of 0.625   mg/day of CEE and 2.5   mg/day of MPA does not appear to prevent CHD. Thus, the authors of the WHI HT trial data made the following recommendations: “Results from WHI indicate that the combined postmenopausal hormones CEE, 0.625   mg/day, plus MPA, 2.5   mg/day, should not be initiated or continued for the primary prevention of CHD. In addition, the substantial risks for cardiovascular disease and breast cancer must be weighed against the benefit for fracture in selecting from the available agents to prevent osteoporosis.”

7. e. To ensure that patients in the placebo arm of the WHI HT trial would continue to participate for the entire study, patients with significant vasomotor symptoms were excluded. Thus, the average participant age at the start of the study was 63   years, with an average of 6   years since the onset of menopause. In addition, quality-of-life indicators, including menopausal symptom relief, were not measured in this trial. For obvious reasons of project cost, recruitment, and statistical power, only one dose and route of one combination formulation of HT were evaluated in this study. All of these limitations may affect the generalizability of this RCT’s results to other HT formulations, dosages, and routes, and they may affect the applicability of these results to younger, symptomatic postmenopausal patients.

8. c. The current FDA indications for ET/HT include the following: (1) treatment of moderate to severe vasomotor symptoms, (2) treatment of moderate to severe symptoms of vulvar and vaginal atrophy (dryness and irritation) associated with menopause, and (3) prevention of postmenopausal osteoporosis. Despite studies, including the WHI HT trial, supporting the effectiveness of ET/HT for prevention of osteoporotic fractures, it is not indicated for the treatment of osteoporosis. Although the Postmenopausal Estrogen/Progesterone Interventions trial and other RCTs have demonstrated the overall favorable lipid effects of ET/HT, it is not indicated for the treatment of hyperlipidemia. ET/HT may benefit urinary symptoms related to urogenital atrophy, but it is not indicated for urge incontinence.

On January 8, 2003, the FDA issued a statement advising women and health care professionals about important safety changes to labeling of all estrogen and estrogen with progestin products for use by postmenopausal women. These changes reflected the FDA’s analysis of data from the WHI that raised concern about risks of using these products. The FDA’s labeling changes include a black box warning that reflects new risk information and changes to the approved indications to emphasize individualized decisions that appropriately balance the potential benefits and risks of these products.

The black box warning, the highest level of warning information in labeling, highlights the increased risks for heart disease, heart attacks, strokes, and breast cancer. This warning also emphasizes that these products are not approved for heart disease prevention. The FDA has also modified the approved indications for ET and HT to clarify that these drugs should be used only when the benefits clearly outweigh risks. Of the three indications, two were revised to include consideration of other therapies. The three indications are as follows:

Stay updated, free articles. Join our Telegram channel

Join