Case of the Month ESAP Special Edition: Women’s Health
Sep 2016
This issue highlights a special edition of ESAP, available for a limited time. Test your clinical knowledge with this free case to discover the rich intellectual legacy of endocrinology. Available on the online store.
Clinical Vignette
A 38-year-old woman is seeking your opinion on whether she is a suitable candidate for restarting combined oral contraceptives containing both estrogenic and progestational agents. In her late teens, she began taking birth control pills for contraception without difficulty, but she stopped them when she and her husband wished to have children. Between pregnancies, she used barrier methods for contraception. She delivered her second daughter 3 months ago. She had a recent conversation with her primary care physician who is opposed to restarting birth control pills; thus, she is seeking a second opinion.
Her most recent pregnancy was complicated by hypertension treated with hydralazine. Her hypertension persisted after delivery and her regimen was switched to metoprolol, which she continues to take at a dosage of 50 mg twice daily. This is her only medication. Otherwise, it was an unremarkable pregnancy with delivery of a healthy, full-term baby. She is not breastfeeding.
Her medical history is unremarkable. She has resumed smoking cigarettes in the past month (1 pack per day), although she had stopped smoking during the pregnancy. She is relatively active. There is no personal or family history of deep venous thrombosis.
On physical examination, her height is 63 in (160 cm) and weight is 161 lb (73.2 kg) (BMI = 28.5 kg/m2). Her blood pressure is 126/78 mm Hg, and pulse rate is 66 beats/min. She has normal findings on cardiovascular and pulmonary examination. On her extremities, she has extensive bilateral venous varicosities without pedal edema. Arterial examination findings are normal.
You agree with her primary care physician that an alternative method of contraception should be selected.
Which of the following characteristics of this patient provides the strongest rationale for that opinion?
Oral contraceptives are one of the most reliable forms of birth control. Theoretical failure rates are well below 0.5%, although issues surrounding adherence probably make the actual failure rate close to 2%. Nonetheless, oral contraceptives are often selected as the first-line method for birth control.
In recent years, there have been multiple reformulations of oral contraceptive pills that have improved tolerability. Lower doses of estrogen have reduced thrombotic and cardiovascular risk. The development of progestational agents with less androgenic and glucocorticoid activity have resulted in preparations with less associated weight gain and potential for developing hirsutism. Additionally, most current oral contraceptives have fewer negative effects on carbohydrate metabolism and can be used more safely in women with diabetes mellitus. Many oral contraceptives are available in generic formulations, so cost has declined as well.
However, the use of oral contraceptives is not risk free. Cardiovascular events remain a concern, although the risk of myocardial infarction is exceedingly rare. Deep venous thrombosis remains a risk to be considered. However, superficial venous varicosities are not associated with an increased risk of venous clotting (thus, Answer D is incorrect). BMI of 25 kg/ m2 or greater is not a contraindication for oral contraceptives (thus, Answer C is incorrect).
The Centers for Disease Control has published a guideline that lists coexisting conditions that place women at increased risk when taking oral contraceptives. Cigarette smoking, hypertension, and postpartum status are all potentially confounding conditions that make use of oral contraceptives contraindicated. Women older than 35 years who smoke more than 15 cigarettes daily are at a higher risk for vascular complications when taking oral contraceptives (thus, Answer A is correct). Clinically significant hypertension is a contraindication as well, although the threshold to strongly consider alternative methods of birth control is a systolic blood pressure greater than 140 mm Hg or a diastolic pressure greater than 90 mm Hg. For patients with a systolic blood pressure greater than 160 mm Hg or a diastolic pressure greater than 100 mm Hg, oral contraceptives are contraindicated. This patient’s hypertension does not meet these criteria and is not an absolute contraindication (thus, Answer B is incorrect). Oral contraceptives are contraindicated in women within the first 21 days after delivery due to the increased risk of hypercoagulation. This risk tends to decrease over time, and in women who are beyond 2 months postpartum, as this patient is, oral contraceptives are considered safe (thus, Answer E is incorrect).
Other conditions that should prevent the practitioner from prescribing oral contraceptives include, but are not limited to, a history of deep venous thrombosis, recent surgery with immobility, systemic lupus erythematosus, diabetic nephropathy (hypercoagulation with renal loss of anticoagulants), organ transplant, history of hepatocellular carcinoma, and hepatic cirrhosis.
Educational Objective: Identify conditions that render the use of oral contraceptives contraindicated.
Historical Context Dr. Gregory G. Pincus, Endocrine Society President 1951-1952
Dr. Gregory Goodwin Pincus (Endocrine Society President 1951-1952) is credited with developing the methods to use exogenous estrogen and progesterone to suppress ovulation. His initial studies led directly to the US FDA approving these as a treatment for “certain menstrual disorders” and eventually as the first birth control pill. His research resulted in more than 200 publications and was the basis for early treatment options for breast cancer and eventually the “morning-after pill.”
Gregory Pincus, described as “a bushy-haired man with a gray mustache and dark, burning eyes,” was born April 9, 1903, in Woodbine, New Jersey. He married Elizabeth Lipman in 1924. Pincus attended Cornell University, graduating with a bachelor’s degree, a master’s degree, and eventually a doctorate of science from that institution. He started his faculty career at Harvard University (1930-1937), during which time he reported the methodology for in vitro fertilization in rabbits. The concept was highly controversial and he received much negative publicity, ending his stint at Harvard and landing him at Clark University in Worchester, Massachusetts, from 1938 to 1946. There, he collaborated with Dr. Hudson Hoagland, studying steroid hormones. During that time he was “woefully underfunded” and was forced to take a job as a janitor in the lab to supplement his meager salary and provide for his wife and 2 children.
Dr. Pincus’s work attracted the attention of Margaret Sanger who, as the director of Planned Parenthood, provided the initial funding for research on the use of steroid hormones as antiovulants. After completing his proof-of-concept studies, Pincus teamed with Dr. M. C. Chang, a senior scientist of the Worcester Foundation, and Dr. John Rock, a gynecologist and fertility expert. They began the work to produce a synthetic progestational agent, screening hundreds of compounds but eventually settling on 3 steroid compounds derived from the roots of the wild Mexican yam. In collaboration with 2 pharmaceutical companies (Syntex and Searle), the 3 “fathers” of birth control pills were able to develop an effective oral contraceptive. The medication was called “Enovid,” combining an estrogen called mestranol with a steroidal progestin called norethynodrel, and the US FDA approved it in 1957. Notably, Dr. Pincus’s initial studies were performed in women in Puerto Rico, as the use of all forms of contraception was illegal in his state of Massachusetts. Later in his career, Dr. Pincus held appointments at Tufts University (1946-1950) and Boston University (1950-1967). He was elected into the National Academy of Sciences, the American Association for the Advancement of Science, and the American Academy of Arts and Sciences. He won the Lasker Award in 1960 and was posthumously elected into the National Inventors Hall of Fame in 2006. Dr. Pincus died of myeloid metaplasia, a rare hematologic malignancy, on August 22, 1967, at the Peter Bent Brigham Hospital.
References: Centers for Disease Control and Prevention. U.S. Medical Eligibility Criteria for Contraceptive Use, 2010. Morbidity Mortality Weekly Report. 2010;Vol 59:1-88.
Reifsnider E, Mendias N, Davila Y, Bever Babendure J. Contraception and the obese woman. J Am Assoc Nurse Pract. 2013;25(5):223-233.
Gill SK. Cardiovascular risk factors and disease in women. Med Clin North Am. 2015;99(3):535-552.
Women with the common reproductive and metabolic condition polycystic ovary syndrome (PCOS) face a greater risk of developing bulimia, binge eating disorder, and disordered eating, according to new research published in The Journal of Clinical Endocrinology & Metabolism. PCOS affects roughly one in eight women. Women who have the condition face an increased risk of developing…
The type of weight loss surgery women undergo before becoming pregnant may affect how much weight their children gain in the first three years of life, according to a study presented at ENDO 2024. Researchers found children born to women who underwent sleeve gastrectomy before they became pregnant gain more weight per month on…