I found Dr. Norton’s article on cell-free DNA (cfDNA) screening for women at low risk for fetal abnormalities to be enlightening and educational. The section addressing cost-effectiveness, however, was somewhat obsolete. The referenced study by Cuckle and colleagues,1 which estimated the cost of cfDNA per case of Down syndrome in low-risk patients at $3.6 million, was published in 2013. With 4 major companies in the market, the cost/benefit ratio has been changing rapidly. At least one company has dropped the cost of the cfDNA test nearly 80% from 2015 to 2016, making the above reference irrelevant. Recently, Ariosa dropped the price of their Harmony cfDNA test to just $119 in our area, regardless of a patient’s insurance or poverty level. This is significantly less than the cost of performing an early screen and is being welcomed by my patients even after substantial counseling on the test’s limitations in the low-risk population. Natera, another laboratory with a similar test, offers a low-cost option. However, patients must provide proof that their income is below a specified level.
Guidelines from the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) likely will have a hard time keeping up with the cost-effectiveness of noninvasive prenatal testing, as the price continues to be dynamic.
Samuel Wolf, DO
Panama City, Florida
Reference
- Cuckle H, Benn P, Pergament E. Maternal cfDNA screening for Down syndrome—a cost sensitivity analysis. Prenat Diagn. 2013;33(7):636–642.
In their expert commentary, Drs. Kaunitz, Manson, and Stuenkel state:
Although findings from this large observational study from Finland suggest that women stopping hormone therapy (HT) experienced elevations in cardiac and stroke mortality within the first year after discontinuation, these associations are not likely to be causal and contradict those of the Women’s Health Initiative, the largest randomized trial of HT, which found no elevated risks after discontinuation of HT.
They support this claim by citing Heiss 2008.1 In fact, however, the Women’s Health Initiative (WHI) data show opposite to their statement: In the WHI, all-cause mortality was increased among the women who were assigned to estrogen-progestin therapy (EPT) relative to those who were assigned to placebo within the 3 years of EPT cessation (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.95–1.39). More importantly, mortality was significantly increased among women who were originally assigned to EPT relative to those who were assigned to placebo and were at least 80% adherent with intervention (HR, 1.53; 95% CI, 1.04–2.24). Thus, the statement by Drs. Kaunitz, Manson, and Stuenkel is incorrect.
In addition to the WHI studies, data are available from at least 2 other randomized controlled trials addressing the issue of HT withdrawal. In the Heart and Estrogen/progestin Replacement Study (HERS) II,2 the unblinded 2.7-year follow-up to the HERS trial, women originally assigned to EPT had a 3.3-fold higher rate of ventricular arrhythmia requiring resuscitation than women assigned to placebo (HR, 3.30; 95% CI, 1.08–10.10). During the first 6 months of posttrial follow-up of the Women’s Estrogen for Stroke Trial (WEST),3 there were 3 fatal strokes and 18 nonfatal strokes among the women originally randomized to estradiol therapy; there were 9 strokes (1 fatal and 8 nonfatal) among the women originally assigned to placebo (HR, 2.3; 95% CI, 1.1–5.0; P = .03).
In our study we detected that women who stopped HT, compared with women who continued HT, had a 2.3-fold (95% CI, 2.12–2.50) greater risk of cardiac death within the first post-HT year and a 1.3-fold (95% CI, 1.21–1.31) greater risk of cardiac death more than 1 year after stopping HT.4 In addition, women who stopped HT, compared with women who continuedHT, had a 2.5-fold (95% CI, 2.28–2.77) greater risk of dying from stroke within the first post-HT year and a 1.3-fold (95% CI, 1.19–1.31) greater risk of dying from stroke more than 1 year after stopping HT. We believe that these data substantially further our understanding of the posttrial data from WHI, as well as HERS and WEST. Thus, cumulative data support that HT withdrawal potentially has detrimental implications for women. In total, the data are highly informative when counseling women regarding use or discontinuation of HT.
Tomi Mikkola, MD
Helsinki, Finland
References
- Heiss G, Wallace R, Anderson GL, et al; WHI investigators. Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA. 2008;299(9):1036–1045.
- Grady D, Herrington D, Bittner V, et al; HERS Research Group. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II) [published correction appears in JAMA. 2002;288(9):1064]. JAMA. 2002;288(1):49–57.
- Viscoli CM, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horwitz RI. A clinical trial of estrogen-replacement therapy after ischemic stroke. N Engl J Med. 2001;345(17):1243–1249.
- Mikkola TS, Tuomikoski P, Lyytinen H, et al. Increased cardiovascular mortality risk in women discontinuing postmenopausal hormone therapy. J Clin Endocrinol Metab. 2015;100(12):4588–4594.
