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Mayo Clin Proc. Jan 2012; 87(1): 89–93.
PMCID: PMC3498101
Clinical Pearls in Women's Health
Lynne T. Shuster,ab[low asterisk] John B. Bundrick,b and Scott C. Litinb
aWomen's Health Clinic, Division of General Internal Medicine, Mayo Clinic, Rochester, MN
bDivision of General Internal Medicine, Mayo Clinic, Rochester, MN
[low asterisk]Correspondence: Address to Lynne T. Shuster, MD, Women's Health Clinic, Division of General Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905
At the 2001 Annual Conference of the American College of Physicians, a new teaching format to aid physician learning, Clinical Pearls, was introduced. Clinical Pearls is designed with the 3 qualities of physician-learners in mind. First, we physicians enjoy learning from cases. Second, we like concise, practical points that we can use in our practice. Finally, we take pleasure in problem solving.
In the Clinical Pearls format, speakers present a number of short cases in their specialty to a general internal medicine audience. Each case is followed by a multiple-choice question answered live by attendees using an audience response system. The answer distribution is shown to attendees. The correct answer is then displayed and the speaker discusses teaching points, clarifying why one answer is most appropriate. Each case presentation ends with a Clinical Pearl, defined as a practical teaching point that is supported by the literature but generally not well known to most internists.
Clinical Pearls is currently one of the most popular sessions at the American College of Physicians meeting. As a service to its readers, Mayo Clinic Proceedings has invited a selected number of these Clinical Pearl presentations to be published in our Concise Reviews for Clinicians section. “Clinical Pearls in Women's Health” is one of them.
A 32-year-old woman in her second trimester of pregnancy is found to have blood pressures ranging from 150-160/90-95 mm Hg on 3 separate occasions during the past 2 weeks. She has no edema, and a urine dipstick test reveals no proteinuria. She has no history of hypertension.
Question
What is the most appropriate next step in management?
  • a 
    Recommend salt restriction and bed rest
  • b 
    Administer a diuretic
  • c 
    Administer methyldopa
  • d 
    Administer lisinopril
  • e 
    Avoid administering an antihypertensive drug if diastolic blood pressures stay below 100 mm Hg
Discussion
Hypertension in pregnancy is a leading cause of maternal and fetal morbidity.1 Hypertensive disorders of pregnancy include preeclampsia-eclampsia, chronic hypertension, preeclampsia superimposed on chronic hypertension, and gestational hypertension.2 This patient appears to have gestational hypertension, characterized by mild to moderate elevation of blood pressure after midgestation but without abnormal proteinuria. She may become preeclamptic and needs to be carefully monitored. She is also at increased risk of hypertension, coronary heart disease, and stroke later in life.3
There are no clear guidelines regarding the treatment of hypertensive disorders of pregnancy, but certain principles apply. The use of antihypertensive medications to reduce maternal blood pressures in gestational hypertension does not prevent preeclampsia or reduce perinatal morbidity, and treatment may result in smaller fetuses. The National High Blood Pressure Education Program and American College of Obstetrics and Gynecology generally suggest withholding antihypertensive drugs when diastolic levels are below 100 mm Hg.2,4
When medication is needed, methyldopa remains a preferred drug for treating gestational hypertension because of its long safety track record.2,4 Increasingly, labetalol or nifedipine, both of which are classified as pregnancy category C, is used. Diuretics are typically avoided because of concern about potentiating plasma volume contraction and impairing placental blood flow. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are fetotoxic.
Sodium restriction is not recommended for gestational hypertension, with or without proteinuria. Bed rest has no demonstrable maternal or fetal benefit with regard to gestational hypertension.
For this patient, a 24-hour urine collection for protein measurement and ultrasonography to evaluate fetal growth would typically be the next step in evaluation. Decisions about these steps and any consideration of antihypertensive therapy need to be made in consultation with the patient's obstetrician.
Clinical Pearl
Goals for the treatment of hypertension in pregnancy differ from those for the general hypertensive population.
A 45-year-old woman presents with changes in her menstrual period along with hot flashes and vaginal dryness. Menstrual periods have changed during the past 9 months, with cycles ranging from 20 to 60 days. She had light vaginal bleeding between the last 2 periods. She requests a prescription for an oral contraceptive to regulate bleeding and reduce hot flashes.
Oral contraceptives were well tolerated in the past. She underwent a tubal ligation at 35 years of age. She is a nonsmoker, has normal lipid levels and blood pressure, but is overweight. She takes no prescription medications.
The findings on her physical examination, including breast and pelvic examination with Papanicolaou test, are normal.
Question
Which one of the following is the most appropriate next step?
  • a 
    Reassure her that the bleeding pattern is typical of perimenopause and prescribe a low-dose oral contraceptive
  • b 
    Reassure her that this bleeding pattern is typical of perimenopause and advise against taking an oral contraceptive
  • c 
    Recommend menopausal hormone therapy because she is in perimenopause
  • d 
    Recommend an endometrial biopsy
  • e 
    Recommend pelvic ultrasonography
Discussion
Irregular menstrual bleeding is typical of perimenopause. Periods may be shorter or longer in duration, and cycles may be shorter or longer in length. Menstrual changes that should prompt concern, however, include the following: cycle intervals of fewer than 21 days; any spotting or bleeding between periods; menstrual bleeding lasting longer than 7 days or 2 or more days longer than usual; very heavy flow, especially with clots; and bleeding after intercourse.5
Pelvic ultrasonography is not sufficient to exclude endometrial cancer in a perimenopausal woman with these changes.6 For any of these menstrual changes, particularly in women aged 45 years and older, endometrial assessment is needed because the rate of endometrial neoplasia begins to increase sharply at this age. If the results of endometrial assessment are negative, a hormonal contraceptive may be prescribed to regulate periods and relieve perimenopausal vasomotor symptoms. Menopausal hormone therapy is less desirable in this circumstance because it does not suppress ovulation and will often be associated with unscheduled, unpredictable vaginal bleeding during perimenopause.
Clinical Pearl
Perimenopause is characterized by menstrual irregularity. Perimenopausal women having cycles of fewer than 21 days, menses lasting more than 7 days, heavy menstrual flow with clots, bleeding between menses, or bleeding occurring after intercourse need endometrial assessment.
A 70-year-old woman reports to your office for reevaluation of hypertension. Her last cervical cytologic screening was 2 years ago, and she reminds you she is due for another Papanicolaou test this year. She is monogamous with her husband of 50 years. Prior screening Papanicolaou tests were performed regularly, including 3 times during the past 10 years, and the results were consistently negative. Family history is notable for cervical cancer in her mother.
Medications include the following: lisinopril, 10 mg daily; calcium with vitamin D, twice daily; multivitamin, once daily; and alendronate sodium, 70 mg once weekly.
Question
Which one of the following should you advise?
  • a 
    Papanicolaou test now and human papillomavirus test
  • b 
    Papanicolaou test now and reflex human papillomavirus test
  • c 
    Papanicolaou test next year
  • d 
    Discontinue Papanicolaou test screening
  • e 
    She may decide for herself how often to undergo Papanicolaou test screening
Discussion
Most new cases of cervical cancer are found in women who have never been screened or who have been infrequently screened. Postmenopausal women with multiple prior consecutive negative Papanicolaou test results are at low risk for cervical cancer.7 In addition, postmenopausal atrophy can predispose patients to false-positive results, potentially leading to unnecessary procedures, discomfort, and expense. The US Preventive Services Task Force recommends against routine screening after the age of 65 years if prior screening was adequate and the woman is not otherwise at high risk for cervical cancer.8 The American College of Obstetrics and Gynecology advises that it is reasonable to discontinue screening at either 65 or 70 years of age in women who have had 3 or more negative cytologic test results in a row and no abnormal test results in the past 10 years.7
A family history of cervical cancer does not affect screening frequency because cervical cancer is associated with human papillomavirus infection and is not a heritable disorder.
Clinical Pearl
Cervical cytologic screening may be discontinued at 65 to 70 years of age in women with previous adequate screening who are not known to be at increased risk for cervical cancer.
A 43-year-old woman, gravida 3, para 3, with very heavy, painful periods seeks your advice. Symptoms did not improve after endometrial ablation. She met with her gynecologist to review treatment options and would like to proceed with a hysterectomy. She has been advised to consider ovary removal along with the hysterectomy and asks for your opinion. She has a history of symptomatic ovarian cysts and premenstrual syndrome. Her family history is notable for a maternal grandmother with ovarian cancer at the age of 80 years.
Question
All of following are risks or benefits of elective oophorectomy at the time of hysterectomy except which one?
  • a 
    Decreased risk of ovarian cancer
  • b 
    Decreased risk of breast cancer
  • c 
    Decreased risk of cognitive dysfunction
  • d 
    Increased risk of cardiovascular disease
  • e 
    Increased risk of depression
Discussion
Prophylactic oophorectomy performed before natural menopause is associated with an increased risk of premature death, cardiovascular disease, cognitive impairment or dementia, parkinsonism, stroke, osteoporosis, symptoms of depression and anxiety, and a decline in sexual function.9 Whether spontaneous or induced, premature menopause (before the age of 40 years) or early menopause (before the age of 45 years) has been reported to be associated with an increased risk for overall mortality, cardiovascular diseases, neurologic diseases, psychiatric diseases, osteoporosis, and other sequelae.10 The risk of adverse outcomes increases with earlier age at the time of menopause. Estrogen mitigates some but not all of these risks.
The health benefit of prophylactic bilateral oophorectomy for reducing the risk of breast, ovarian, and fallopian tube cancers in women known to be at increased risk is well established. However, benefits for cancer risk reduction in other women should be weighed against the long-term effects of loss of ovarian function. Having one second-degree relative with ovarian cancer late in life does not appreciably increase the risk of ovarian cancer.
Clinical Pearl
The long-term health risks of prophylactic oophorectomy should be carefully weighed against the benefits for reducing the risk of ovarian cancer in women at average risk.
A 28-year-old woman presents for refill of her birth control pill prescription. She started taking birth control pills 1 year ago for contraception and to control heavy periods. Since then she has experienced several episodes of a severe headache during the first 2 days of the pill-free week monthly. Headaches are preceded by visual symptoms consisting of a black spot surrounded by flashing lights, enlarging during approximately 30 minutes and then fading away, and then followed by a left-sided headache, lasting for 6 to 8 hours. She experiences nausea and light sensitivity with the headaches. She generally takes an over-the-counter headache analgesic and goes to bed. She would like to continue taking birth control pills but wonders what she can do for the headaches. Her medical history is negative for migraines.
Her current medications include the following: combined ethinyl estradiol and norgestimate once daily for 21 consecutive days followed by 7 days of placebo; and combined acetaminophen, 250 mg, aspirin, 250 mg, and caffeine, 65 mg, 2 at onset of headache.
Her physical examination findings are as follows: blood pressure, 110/62 mm Hg; pulse, 88/min; and heart, lung, abdomen, breast, pelvis, and neurologic examination negative for abnormalities.
Question
Which one of the following is the best management plan for this patient?
  • a 
    Switch to monophasic combined oral contraceptive regimen
  • b 
    Add low-dose estrogen patch during the pill-free week each month
  • c 
    Switch to extended-cycle combined oral contraceptive regimen (eg, 1 pill taken every day consecutively, with no pill-free interval)
  • d 
    Take sumatriptan at onset of headache
  • e 
    Stop use of combined oral contraceptive and consider alternative birth control method
Discussion
The new onset or exacerbation of migraine or the development of headache with a new pattern of occurrence, increased severity, or association with focal neurologic symptoms warrants discontinued use of a combined (estrogen plus progestogen) oral contraceptive.11 Women with migraine who use oral contraceptives are at a 2- to 4-fold increased risk of ischemic stroke compared with women with migraines who do not use oral contraceptives.12 Current data do not allow differentiation of risk by type of oral contraceptive or by type of migraine, but the baseline risk of stroke is higher for women who have migraine with aura compared with migraine without aura.12 Current recommendations are that combined oral contraceptives may be considered for women younger than 35 years who have migraine without aura, do not smoke, and are otherwise healthy because the absolute risk of stroke in this group is very low.11
If this woman had a previous history of migraine and uncomplicated migraine symptoms appeared during the pill-free week, management options would include adding a triptan when needed for symptoms, bridging with transdermal estrogen during the pill-free week, or switching to an extended-cycle pill regimen.13 There is no proven benefit to the common practice of switching from triphasic to monophasic oral contraceptives in an effort to reduce headaches.
Clinical Pearl
Women who have migraine with aura should avoid combined oral contraceptives. Women taking combined oral contraceptives who develop new onset of migraine, particularly with focal neurologic symptoms, should not continue taking the combination oral contraceptive.
A 34-year-old woman presents with heavy menses during the past 2 years. Her menstrual periods occur monthly and last 4 to 5 days. She has heavy bleeding with clots and cramping discomfort on the first 2 days. For several days before her periods she experiences mood irritability and breast tenderness. She is otherwise healthy.
She takes an iron supplement and no other medications. There is no family history of cancer. She would prefer not to take any estrogen-containing treatments and would prefer to avoid invasive procedures.
Her blood pressure is 105/60 mm Hg, and her physical examination findings are normal. Her hemoglobin level is 11.4 g/dL (to convert to g/L, multiply by 10), with a mean corpuscular volume of 80 fL (to convert to μm3, divide by 1). Her serum creatinine level is 0.7 mg/dL (to convert to μmol/L, multiply by 88.4). Her thyrotropin level is normal.
Question
Which one of the following treatments would be most preferred to reduce the volume of her menorrhagia?
  • a 
    Misoprostol
  • b 
    Raloxifene
  • c 
    Low-dose luteal phase progestogen
  • d 
    Naproxen
  • e 
    Danazol
Discussion
Heavy menstrual bleeding (>80 mL/d) is common, occurring in approximately 10% of women during the reproductive years. In premenopausal women with a regular, ovulatory pattern of heavy bleeding, virtually all cases with an identified cause are related to benign abnormalities, such as fibroids and endometrial polyps. Most are idiopathic and amenable to medical therapy.
Common medical treatments include oral contraceptives, which appear to be effective in small trials but have not been studied in large randomized trials. Danazol and tranexamic acid are effective but not commonly used because of their adverse effects and cost. The levonorgestrel-releasing intrauterine device is effective and well tolerated but is generally not used as a first-line option.
Many women (as in the present case) prefer a more conservative option, and nonsteroidal anti-inflammatory drugs (NSAIDs) are well suited for this purpose. Although widely known to be useful in ameliorating menstrual cramps, the prostaglandin inhibition also produces a significant reduction in menstrual flow. Naproxen and mefenamic acid have been best studied, and the typical dose of naproxen is 500 mg twice daily for the first 2 days, followed by 250 mg 3 times daily for up to 5 days. In most trials, NSAIDs are associated with a 25% to 30% reduction in menstrual blood flow. Subjective improvements are more substantial, with women being 10 times as likely to report an improvement in their menstrual symptoms while taking NSAIDs compared with placebo.14 Low-dose luteal phase progestogens, taken on days 15 to 26 of the menstrual cycle, appear to be less effective than NSAIDs in treating ovulatory bleeding and could worsen the patient's premenstrual breast tenderness and irritable mood. Misoprostol is a prostaglandin analogue and would be expected to worsen this patient's symptoms. Raloxifene is a selective estrogen receptor modifier that is relatively neutral in its effect on the endometrium and has no role in the management of menstrual problems.
Clinical Pearl
In women with heavy menstrual bleeding, NSAIDs may reduce both discomfort and menstrual flow.
Footnotes
See end of article for correct answers to questions.
CORRECT ANSWERS: Case 1: e, Case 2: d, Case 3: d, Case 4: c, Case 5: e, Case 6: d
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2. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000;183(1):S1–S22. [PubMed]
3. Garovic V.D., Bailey K.R., Boerwinkle E. Hypertension in pregnancy as a risk factor for cardiovascular disease later in life. J Hypertens. 2010;28(4):826–833. [PMC free article] [PubMed]
4. ACOG Committee on Practice Bulletins ACOG Practice Bulletin, No. 29; chronic hypertension in pregnancy. Obstet Gynecol. 2001;98(1):177–185. [PubMed]
5. North American Menopause Society 4th ed. North American Menopause Society; Mayfield, Heights, OH: 2010. Menopause Practice: A Clinician's Guide.
6. Kaunitz A.M. Gynecologic problems of the perimenopause: evaluation and treatment. Obstet Gynecol Clin North Am. 2002;29(3):455–473. [PubMed]
7. ACOG Committee on Practice Bulletins–Gynecology ACOG Practice Bulletin no. 109: cervical cytology screening. Obstet Gynecol. 2009;114(6):1409–1420. [PubMed]
8. US Preventive Services Task Force Recommendations and Rationale: Screening for Cervical Cancer. http://www.uspreventiveservicestaskforce.org/3rduspstf/cervcan/cervcanrr.pdf Accessed August 30, 2011. [PubMed]
9. Shuster L.T., Gostout B.S., Grossardt B.R., Rocca W.A. Prophylactic oophorectomy in premenopausal women and long-term health. Menopause Int. 2008;14(3):111–116. [PMC free article] [PubMed]
10. Shuster L.T., Rhodes D.J., Gostout B.S., Grossardt B.R., Rocca W.A. Premature menopause or early menopause: long-term health consequences. Maturitas. 2010;65(2):161–166. [PMC free article] [PubMed]
11. World Health Organization 4th ed. World Health Organization; Geneva, Switzerland: 2010. Medical Eligibility Criteria for Contraceptive Use.
12. Curtis K.M., Mohllajee A.P., Peterson H.B. Use of combined oral contraceptives among women with migraine and nonmigrainous headaches: a systematic review. Contraception. 2006;73(2):189–194. [PubMed]
13. Shuster L.T., Faubion S.S., Sood R., Casey P.M. Hormonal manipulation strategies in the management of menstrual migraine and other hormonally related headaches. Curr Neurol Neurosci Rep. 2011;11(2):131–138. [PubMed]
14. Lethaby A., Augood C., Duckitt K., Farquhar C. Nonsteroidal anti-inflammatory drugs for heavy menstrual bleeding. Cochrane Database Syst Rev. 2007;(4) CD000400. [PubMed]
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