PANCE Blueprint Reproductive System (7%)

Menopause

Patient will present as → a 52-year-old female with no menses for 12 months she also complains of hot flushes and dyspareunia

Menopause is a clinical diagnosis and is defined by

  • Cessation of menses for at least 12 months
  • FSH > 30 (although not necessary for diagnosis)

Perimenopause – the transition between reproductive capability and menopause hallmark is irregular menstrual function, lasts 3-5 years

Average age 51.5 years (44-55 years old)

  • On average women will spend 30+ years in the postmenopausal state
  • Onset < 40 years old = premature ovarian failure
In normal healthy women over age 45 we diagnose menopause as 12 months of amenorrhea in the absence of other biological or physiological causes. A high serum FSH is not required to make the diagnosis.

For health women 45 +

FSH and estradiol levels (FSH > 30) with ↓ estradiol

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

Women 40 - 45 years who present with irregular menstrual cycles and menopausal symptoms may be in the menopausal transition

  • Same endocrine evaluation as for any woman with oligo/amenorrhea: serum human chorionic gonadotropin (hCG), prolactin, TSH, FSH 

Women under age 40 years with irregular menses and menopausal symptoms,

  • Complete evaluation for premature ovarian failure

Hormonal Therapy: Estrogen and Progesterone replacement – Only indicated in symptomatic women

If uterus - HRT (estrogen + progesterone), if no uterus (ERT)

  • For women who have had a hysterectomy, estrogen is used alone
    • Oral, transdermal (patch, lotion, spray, or gel), or vaginal forms may be used. Treatment should start with the lowest dose; the dose is increased every 2 to 4 wk as needed.
    • Low doses include 0.3 mg PO once/day (conjugated equine or synthetic estrogens), 0.5 mg PO once/day (oral estradiol), and 0.025 mg once/day (estradiol patch)
  • Women who have a uterus should be given progestin in addition to estrogen because unopposed estrogen increases the risk of endometrial cancer. The progestin is taken with estrogen continuously (ie, daily) or sequentially (12 to 14 consecutive days of every 4 wks)
Know the contraindications for HRT

For vaginal dryness, recommend vaginal stimulation and OTC vaginal lubricants and moisturizers, and if they are ineffective, prescribe low-dose vaginal estrogen creams, tablets, or rings.

Non-hormonal therapies: Cool temperatures, avoid hot, spicy foods or beverages, avoid ETOH, exercise, soy

  • Alternative drugs for vasomotor symptoms
    • SSRIs (paroxetine)
    • SNRIs
    • clonidine
    • gabapentin

IM_MED_MenopauseSymptomsHAVOC_v1.3_ Menopause is described by decreased estrogen production due to age-linked decline in ovarian follicles. It is defined as one whole year without ovulation, and the average age of menopause is 51 years old. Symptoms can be remembered with the HAVOCS mnemonic: Hot flashes, Atrophy of the Vagina, Osteoporosis, Coronary artery disease and Sleep disturbances.

Question 1
A 51-year-old woman has been experiencing progressive symptoms of profuse night sweats and frequent hot flushes occurring both day and night. She finds her emotional state increasingly labile. She is also experiencing sleep disturbances and anxiety. She denies any other complaints. Her last period was approximately 12 months ago. She has no history of medical problems or affective disorders. Her pulse is 78 beats/ minute, and her blood pressure is 122/ 74 mm Hg. Her pelvic examination reveals atrophic external genitalia, a small anteverted uterus, and no adnexal masses. The rest of her examination is completely normal. What is the most likely diagnosis in this patient?  
A
pheochromocytoma
B
hyperthyroidism
C
menopause
D
generalized anxiety disorder
E
panic attacks
Question 1 Explanation: 
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.
Question 2
What is the most effective treatment option for this patient?
A
thyroid hormone replacement
Hint:
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).
B
estrogen with progestin therapy (hormone therapy [HT])
C
antidepressants
Hint:
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.
D
estrogen alone (estrogen therapy [ET])
Hint:
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.
E
progestin/ progesterone alone
Hint:
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.
Question 2 Explanation: 
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.
Question 3
The HT arm of the Women’s Health Initiative (WHI) trial was stopped prematurely, primarily because patients in the treatment group demonstrated an increased relative risk for
A
breast cancer
B
endometrial cancer
C
colon cancer
D
osteoporotic fractures
E
all of the above
Question 3 Explanation: 
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. 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.
Question 4
What conclusion can be accurately made on the basis of the findings of the WHI trial?
A
combined equine estrogen (CEE) appears to cause breast cancer
B
CEE appears to cause coronary heart disease (CHD)
C
medroxyprogesterone acetate appears to cause breast cancer
D
medroxyprogesterone acetate appears to cause CHD
E
daily combined use of 0.625 mg CEE and 2.5 mg medroxyprogesterone acetate progesterone (MPA) should not be initiated or continued for the primary prevention of CHD
Question 4 Explanation: 
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.”
Question 5
If this patient was also complaining of vaginal dryness, reasonable treatment options would include
A
intravaginal estrogen creams or tablets
B
an intravaginal estrogen ring
C
vaginal moisturizers
D
increased foreplay and intercourse
E
all of the above
Question 5 Explanation: 
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.
Question 6
Alternative therapy( ies), with demonstrated efficacy, for this patient’s condition might include
A
black cohosh
B
soy isoflavones
C
red clover
D
selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitor (SSNRIs)
E
all of the above
Question 6 Explanation: 
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.
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