Contraception: What's Most Effective?

From Medscape Ob/Gyn > Viewpoints

Posted: 07/03/2012Peter Kovacs, MD, PhD

Effectiveness of Long-Acting Reversible Contraception

Winner B, Peipert JF, Zhao Q, et al
N Engl J Med. 2012;366:1998-2007

Contraceptive Methods

Contraception is used for 2 reasons. First for birth control, but also because most methods offer noncontraceptive benefits. For example, oral contraceptives can be used to manage hirsutism, dysmenorrhea, and menorrhagia; a progesterone intrauterine device (IUD) is also highly effective in treating menorrhagia.

The efficacy of different contraceptive methods in preventing pregnancy varies and is influenced by whether the method is used "perfectly" or "typically." The efficacy of a few methods of contraception (tubal ligation, subdermal implants) is independent of the user, but most methods are dependent on the level of compliance. Compliance is generally not perfect; therefore, in a small proportion of users, the contraceptive method will fail and pregnancy can ensue. Contraceptive failure is the most common reason for undesired pregnancy. About half of all pregnancies are unplanned, and about half of these are terminated. This puts the patient at risk and is associated with psychological consequences and significant healthcare expenses

Women can select from numerous contraceptive options. Patients with different backgrounds (eg, age, socioeconomic status, education, parity) typically choose different methods, but the healthcare provider plays an equally important role in decision-making. Contraception is expensive; therefore, insurance coverage also influences the decision.

The study by Winner and colleagues compared the efficacy of long-acting, reversible methods of contraception (subdermal implant, IUD) in a large group of women at risk for pregnancy with that of depot medroxyprogesterone acetate injection (DMPA; Depo-Provera®; Pfizer, New York, New York) and other shorter-acting hormone preparations (pill, patch, vaginal ring).

Study Summary

A total of 7486 women participated in the study. All contraceptive methods were free for 2-3 years. The patient was allowed to select the method (and to switch methods if needed) after appropriate counseling. Conception that occurred while using the method was considered a contraceptive failure.

Women who chose the pill, patch, or ring were more likely to be nulliparous and to have private insurance. These women also had fewer previous unintended pregnancies. DMPA users were more likely to be black and to have less education and lower socioeconomic status. Women who selected IUDs or implants were more likely to be older and to be parous.

During the study period, the participants had a total of 156 unintended pregnancies. These women were younger, had lower socioeconomic status, were more likely to be black, and were more likely to have previous undesired pregnancies. Women who used IUDs or implants had a level of risk for unintended pregnancy similar to that of DMPA users. Risk for unintended pregnancy was significantly higher in pill, patch,and ring users (hazard ratio. 21; 95% confidence interval, 13.67-34.88). Younger (under 21 years of age) pill users had a 2-fold increased risk for unintended pregnancy than older pill users. Winner and colleagues concluded that the effectiveness of long-acting reversible contraception is superior to that of the contraceptive pill, patch, or ring and is not altered in adolescents and young women.

Viewpoint

No contraceptive method provides 100% efficacy, but with perfect use, hormonal contraception, long-acting implants, IUDs, and tubal ligation are associated with failure rates of less than 1%. Most methods are associated with higher failure rates with ordinary (typical) use.

The choice of contraception depends on several factors. Reversibility and interference with everyday life are important considerations for some women, whereas other women need a method that also protects them from sexually transmitted infections. Multiparous women typically choose longer-acting methods or may decide on tubal ligation. Parous women also more often select IUDs. Younger women are more likely to choose short-acting hormonal or barrier contraception. They are also more likely to be noncompliant and thus at higher risk for unintended pregnancy. Multiparous women tend to be more compliant, and because pregnancy rates also decline with age, the risk for undesired pregnancy diminishes over time.

Unintended pregnancies should be prevented in all age groups, and especially among nulliparous women who tend to have more psychological consequences. Longer-acting methods that are less user-dependent may be the best options for these women. In well-screened cases, IUDs or subdermal implants may be good choices. DMPA is another option, but the patient needs to be educated about the potential side effects to improve long-term compliance. All women who select long-acting methods should be educated about the prevention of sexually transmitted infections because these options do not protect against these diseases.

Finally, the method must be affordable to the patient. Inability to pay might be a reason for lack of contraception or noncompliance. The costs of contraception should be balanced against the expenses associated with pregnancy termination. This study shows the huge difference in unintended pregnancy rates with short- and long-acting contraceptive methods in favor of the long-acting methods. Counseling should include a discussion of the benefits of long-acting reversible contraception when patients seek medical advice with regard to their contraceptive options
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Cervical Cancer Screening guidelines

From Medscape Ob/Gyn > Kaunitz on Women's Health

Updated Guidelines for Cervical Cancer Screening: Less Is More

Andrew Kaunitz, MD

Posted: 04/05/2012

Hello. I'm Andrew Kaunitz, Professor and Associate Chair of the Department of Obstetrics and Gynecology at the University of Florida College of Medicine in Jacksonville, Florida. Today, I'd like to discuss Updated Guidelines for Cervical Cancer Screening: Less Is More.

The profound impact that annual pap smears have made in reducing the incidence of and mortality from cervical cancer represents a triumph of preventive medicine. Over time, we have learned that beginning screening at age 21 years and performing cytology less often than annually will not compromise outcomes. We also have come to appreciate the role human papillomavirus (HPV) plays in causing cervical neoplasia.

Over the last decade, cotesting, which employs cytology along with testing for 12 or 13 oncogenic HPV types, has been found to be superior to cytology alone in identifying preinvasive lesions in women older than 30 years of age, while allowing women with negative cytology and HPV results to be safely screened less often.

The American Cancer Society (ACS), the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) have now published new, evidence-based guidelines that will change how we screen for cervical cancer.^[2] To summarize:

• Screening should begin at age 21 years. Cytology alone is recommended every 3 years for women 21-29 years of age.
• For women 30-65 years of age, cotesting every 5 years is recommended. If HPV testing is not available, cytology alone should be continued every 3 years.
• Cytologic findings of atypical squamous cells of undetermined significance (ASCUS) accompanied by HPV-negative results should be managed the same as with a normal screening result.

I anticipate the greatest confusion will surround the management of women who are cytology negative but HPV-positive:

• Option #1 in this setting is to repeat cotesting in 1 year. At that time, women who retest HPV-positive or have low-grade squamous intraepithelial lesion changes on cytology should undergo colposcopy. Women with normal or ASCUS cytology and who are HPV-negative at 1 year should return to routine screening.
• Option #2 is immediate testing for HPV types 16 and 18. Women who test positive for either of these viral types should undergo colposcopy. Women who test negative for both of these viral types should be cotested in 12 months, with management of results as outlined in Option #1.

Women with all other abnormalities should be managed as per existing guidance from ASCCP^]

Most women can discontinue screening after age 65 years or after hysterectomy. Once discontinued, screening should not resume even if a woman reports having a new sexual partner.

Following spontaneous regression or appropriate treatment, women with a history of CIN2 (cervical intraepithelial neoplasia grade 2) or a more severe lesion should continue screening for at least 20 years, even if this extends beyond age 65 years.

New recommendations issued by the US Preventive Services Task Force^[4] are now similar to the updated guidance from ACS/ASCCP/ASCP that is summarized here.

As we implement these new guidelines in our practices, our challenge as women's health clinicians will include educating our patients not only that cervical cancer screening can be performed less frequently without placing them at risk, but also that well-woman visits and pelvic examinations provide health benefits above and beyond early detection of cervical cancer.

Breast Cancer n Underarm Products

From Medscape Medical News > Oncology

Link Between Parabens and Breast Cancer?

Roxanne Nelson

January 26, 2012 — Can the use of antiperspirants and deodorants increase the risk for breast cancer?

Data from a study published online January 12 in the Journal of Applied Toxicology could relieve some of the fears about using underarm products, but could also raise questions and concerns.

The issue centers on exposure to alkyl esters of p-hydroxybenzoic acid (parabens), which are widely used as antimicrobial preservatives in pharmaceuticals, foods, and cosmetics. About 10 years ago, note the researchers, studies began to reveal that parabens had estrogenic properties, and estrogen plays a central role in the development, growth, and progression of breast cancer.

In this new study, researchers in the United Kingdom examined 160 breast-tissue samples obtained from 40 patients who had undergone a mastectomy for primary breast cancer. They found that 99% of samples had traces of at least 1 paraben, and that 60% had traces of 5 different parabens.

Importantly, 7 of the women reported never having used underarm products. This suggests that the parabens originated from another source, note the authors.

The source of the parabens measured in this and in previous studies cannot be identified; it is also not clear if the paraben traces come from long-term accumulation, current exposure, or a combination of both.

Parabens are only one part of a much bigger picture.

"I do think that the parabens are only one part of a much bigger picture," said lead author Philippa D. Darbre, PhD, a reader in oncology at the University of Reading, United Kingdom.

"That is not to say that they do not contribute, but the issue is bigger," she told Medscape Medical News. "Parabens are only one component...of personal care products. What is needed now is...a map of what chemicals there are in a human breast in the modern world and how they distribute across the breast, especially in relation to the site of the tumor."

Adding to the Evidence

In their study, Dr. Darbre and colleagues found a disproportionate incidence of breast cancer in the upper outer quadrant of the breast. In all 40 women, levels of n-propylparaben were higher in the axilla region than in the mid or medial regions (Wilcoxon matched pairs test, P = .004 and P = .021, respectively).

This finding is not unusual; a number of studies over the past several decades have reported that a disproportionately high number of breast tumors in women originate in the upper outer quadrant of the breast, "for which a definitive explanation remains lacking," the authors write. This disproportionality has been increasing in the United Kingdom, and now exceeds 50% of breast cancers.

"The detection of intact esters is more suggestive of a dermal route of exposure," said Philip W. Harvey PhD, a registered toxicologist at Covance Laboratories Ltd, North Yorkshire, United Kingdom, who was not involved in the study. "Oral exposure results in the rapid conversion of the esters to the common metabolite p-hydroxybenzoic acid in both gut and liver. The skin has a much lower esterase capacity, which may explain the fact that 5 different intact paraben esters were found."

Dr. Harvey told Medscape Medical News that the gradient or differential concentrations between zones with the highest levels in the axilla are consistent with a dermal route of exposure. "If the residues derive from dermal sources, the highest concentrations are likely to be at the site of exposure," said Dr. Harvey, who is editor-in-chief of the Journal of Toxicology. "That the axilla shows the highest concentrations is consistent with local application and implicates any products applied there."

He emphasized that Dr. Darbre and colleagues did not investigate causal mechanisms of breast cancer, and did not claim that either parabens or underarm products actually caused the cancer in the patients studied. "However, it does add to the dataset that these weakly estrogenic chemicals are found in significant quantities in estrogen-sensitive tissue," he noted. "Not all women will be sensitive to this, but...there will be a proportion of women who are sensitive."

Causal Relationship Undetermined

Personal care products have been used since the days of Cleopatra, but unprecedented quantities are being used nowadays, and are ultimately being released into the environment, explained Dr. Darbre. Investigations have shown that there is widespread aquatic environmental pollution stemming from use, and therefore little doubt that these chemicals are entering human tissues. The human breast has "become a sink for lipophilic compounds due to its high adipose tissue content," she said.

However, in a previous paper, Dr. Darbre and colleagues pointed out that it remains to be determined whether there is any causal relation between individual or combinations of chemicals and the development of breast cancer (CML Breast Cancer. 2010;22:113-122). The real environmental impact of estrogenic chemicals needs to comprise the entire chemical load in the breast.

An increasing number of environmental chemicals with estrogenic properties have been measured in human breast tissues, the authors of that paper write, which shows that the human breast is exposed to many estrogenic compounds in low doses and over a long period of time. These chemicals could act synergistically to "produce an estrogenic stimulus even at concentrations at which each alone would be ineffective."

There is a gap in our understanding of the combined effect of different chemicals in a single human breast, the authors note, because reports of measurements to date have generally evaluated only single groups of chemicals in any one study group.

"In the meantime, I remain rather ambivalent about hounding just one chemical," said Dr. Darbre. "My advice remains as always — to cut down on, or cut out as much as possible, overall use of personal care products, especially those left on the skin around the breast area."

"When even the water systems are now having to remove personal care product compounds from them, we must be simply using too much in the modern world — too much for our own bodies and too much even for the environment," she added. "The only way forward at the moment is for us all to cut down."

Higher Levels Seen

In this study, Dr. Darbre and her team measured the concentrations of 5 parabens at 4 serial locations in the human breast, from the axilla to the sternum, using tissue samples collected in from 2005 to 2008.

The authors found that at least 1 paraben ester was quantifiable in 158 of 160 specimens (99%), and that all 5 esters were quantifiable in 96 of 160 specimens (60%).

The overall median value for total parabens in the breast tissue was 85.5 ng/g (range, 0.0 to 5134.5 ng/g). This level is 4 times higher than the 20.6 ng/g seen in a smaller previous study, which was also led Dr. Darbre (J Appl Toxicol. 2004;24:5-13).

The highest values were observed for n-propylparaben, at 16.8 ng/g (range, 0.0 to 2052.7), and methylparaben, at 16.6 ng/g (range, 0.0 to 5102.9). They were much lower for n-butylparaben, at 5.8 ng/g (range, 0.0 to 95.4), ethylparaben, at 3.4 ng/g (range, 0.0 to 499.7), and isobutylparaben, at 2.1 ng/g (range, 0.0 to 802.9).

More Research Needed

Dr. Harvey noted that the dataset is sparse and there is a need for further research. "The rising incidence of breast cancer in recent decades points to environmental or lifestyle factors, and chemical exposure — of which the cosmetics scenario is one of the most obvious for direct dermal exposure — is just one implicated factor, together with all the other known factors for breast cancer," he said.

In addition, the regulatory toxicology dataset on parabens as a whole needs to be updated, he added, noting that European regulators are slowly taking steps on information that is coming to light, specifically reducing permitted concentrations of some paraben esters.

"The wisdom of putting estrogenic chemicals in any dermal product must be questioned, particularly compounds with an old regulatory toxicology dataset that probably does not achieve adequate modern standards, and particularly where current-use patterns already indicate that there is insufficient margins of safety in some groups, such as children," Dr. Harvey said.

It is easy to say that there is no evidence of parabens or cosmetics being associated with a health effect if the research has not been done.

"The whole area is poorly researched, but it's now time to coordinate funding and support into a few key areas of environmental endocrine disruption and human health, and the cosmetics scenario is one of the most promising to study in a controlled way," he emphasized. "It is easy to say that there is no evidence of parabens or cosmetics being associated with a health effect if the research has not been done; indeed, the statement is misleading to the public."

Michael J. Thun, MD, vice president emeritus of epidemiology and surveillance research at the American Cancer Society, cautioned that this analysis not be misinterpreted. "The purpose was not to study whether parabens in general or underarm deodorants affect breast cancer risk," he said. "Rather, it examined the levels and anatomic distribution of various paraben compounds in the excised breasts of 40 women with breast cancer."

However, he agrees that more research is needed. "Questions have been raised about their safety because parabens are absorbed through the skin and trace amounts can be detected in tissues, including breast tissue," he explained. "Parabens weakly mimic the effects of estrogen, a hormone known to play a role in breast cancer. No study has yet shown that the concentration of parabens in breast tissue taken from women with breast cancer are higher than that in breast tissue of women without breast cancer. A well-designed study of this issue would be useful."

The Genesis Breast Cancer Prevention Appeal funded the salary of a clinical research fellow and the cost of the liquid chromatography–tandem mass spectrometry analysis. The authors have disclosed no relevant financial relationships.

J Appl Toxicol. Published online January 12, 2012. Abstract

Antirheumatic Drugs and Pregnancy: A Primer

From Medscape Rheumatology > Ask the ExpertsAntirheumatic Drugs and Pregnancy: A Primer Robert I. Fox, MD, PhD Posted: 12/13/2011 Question In a patient taking methotrexate (MTX) for psoriatic arthritis or rheumatoid arthritis, how long of a washout period should be considered before she can safely attempt to conceive? Is there any published information on the long-term use of MTX being related to birth defects or abnormal deliveries once MTX is stopped? Response from Robert I. Fox, MD, PhD Chief, Rheumatology Clinic, Scripps Memorial Hospital, La Jolla, California Women taking methotrexate for arthritis should discontinue this drug and use contraception for at least 3 months before conception based on the recommendations of the American College of Rheumatology. There have been several published studies in the older literature that suggest that for structural anomalies, the critical time interval off methotrexate is from 8 to 10 weeks after the first day of the last menstrual period and the critical dose associated with fetal defects is ≥ 10 mg/week. MTX is a potent abortifacient, and its use during pregnancy is associated with multiple skeletal abnormalities. Methotrexate-induced developmental toxicity is strongly related to when the drug is given and also the dose. There is no evidence that the duration of treatment or the "net total dose" is a predictor of miscarriage or fetal malformation. What About Other Antirheumatic Therapies? Several other examples of antirheumatic therapy and pregnancy are reviewed below: Hydroxychloroquine crosses the placenta. However, there does not appear to be fetal toxicity with hydroxychloroquine doses used for the treatment of connective tissue disorders. Leflunomide (LEF) was teratogenic in animal models, and effective contraception is essential for women of childbearing potential for whom LEF is prescribed. LEF is considered by the US Food and Drug Administration as a "Category X" drug in terms of the risks associated with its use in pregnancy. LEF-treated patients should "wash out" drug using cholestyramine and then wait at least 90 days before attempting pregnancy. Infliximab: According to the manufacturer's prescribing information, infliximab should be given to a pregnant woman only if clearly needed. This information is available at http://www.remicade.com/remicade/assets/HCP_PPI.pdf. However, no maternal toxicity, embryotoxicity, or teratogenicity to infliximab was observed in a murine toxicity model conducted by the manufacturer. Rates of live births, miscarriages, and therapeutic terminations do not appear to be significantly different in women exposed to infliximab during pregnancy according to a registry maintained to track birth defects in women receiving tumor necrosis factor inhibitors during pregnancy. Adalimumab: Studies in monkeys have not revealed harm to the fetus when adalimumab was given during pregnancy. There are no well-controlled studies in humans. Certolizumab pegol: There are no well-controlled studies of certolizumab pegol in pregnant or lactating women. Studies in rats showed that pegylated Fab fragments did not cross the placenta and did not reveal evidence of harm to the fetus. However, exposure to certolizumab pegol during pregnancy is too limited to draw any conclusions.