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Among lactating women during the first postpartum year, the contraceptive efficacy and safety of the 3-month progesterone vaginal ring (PVR) is comparable to the Copper-T380A intrauterine device (IUD), which lasts up to 12 years, according to a multicenter study in India.

The open-label study enrolled 789 healthy, married lactating women (aged 20 to 35 years; mean age 24) at 20 centers in India. All the women were 6 to 9 weeks postpartum following the birth of a normal, healthy infant, exclusively breastfeeding and willing to continue breastfeeding at least four times daily for 1 year. 

Participants also had not used any contraceptives since delivery, but were at risk for pregnancy.

Of the women, 459 used the PVR and 330 the IUD. No significant difference was seen between the two groups in 1-year pregnancy rates using either the Pearl Index (PI) for incidence of pregnancy per 100 women-years nor Kaplan-Meier (K-M) life tables. (PI: 0.62 for PVR and 0.35 for IUD vs. for K-M: 0.7 for PVR and 0.4 for IUD (

Overall, 99.3% of PVR users and 99.6% of IUD users avoided pregnancy. But contraceptive continuation rates at 12 months were 78.5% for IUD compared to only 56.9% for the PVR (

“This outcome was due primarily to expulsions that occurred during toileting and other squatting activities within the first three months and non-replacement of lost rings consistent with the protocol, a stipulation that limited comparisons and comparability of the two study arms,” the authors wrote.

Ring expulsions and menorrhagia were the two most common reasons for discontinuation among PVR and IUD users, respectively. However, few women (4 PVR users and 0 IUD users) reported weaning as a reason for discontinuation.

Median duration of amenorrhea among PVR users was 405 days versus 120 days for IUD users (

 < 0.001). Infants from both groups were fed seven to 12 times daily and grew at expected rates. The study underscores the value of PVR as a method that promotes breastfeeding as being beneficial to infant health.

Both groups reported similar treatment-emergent adverse events (TEAEs): 24.2% of PRV users and 23.0% of IUD users. Five PVR users experienced severe TEAEs: three cases of menorrhagia and one case each of dizziness and vaginal ulceration. This compared to three IUD users with severe TEAEs: one each of extremity pain, seizure and menometrorrhagia/menorrhagia.

Ensuring access to safe and effective contraception for postpartum women is an important national goal for India because only one-quarter of the country’s postpartum population is using contraception. In addition, short pregnancy intervals increase the risks of adverse maternal and infant outcomes.

In 2015, the World Health Organization (WHO) said that women who breastfeed and are 4 or more weeks postpartum can use the PVR without restriction. The authors concluded that a user-controlled device like the PVR “offers an additional contraceptive choice for lactating women for one-year postpartum use and can help to address the unmet need for contraception among postpartum women while encouraging breastfeeding to enhance infant growth and well-being.”

Roy M, Hazra A, Merkataz R, et al. Progesterone vaginal ring as a new contraceptive option for lactating mothers: evidence from a multicenter non-randomized comparative clinical trial in India. Contraception. Published online May 1, 2020. doi:org/10.1016/j.contraception.2020.04.016

Articles

Ensuring access to safe and effective contraception for postpartum women is an important national goal for India because only one-quarter of the country’s postpartum population is using contraception. 

Progesterone vaginal ring for contraception during lactation 

In women with breast cancer, a history of taking menopausal hormone therapy (MHT) before diagnosis was associated with a 23% to 43% reduction in risk of all-cause mortality and mortality from breast cancer and cardiovascular disease (CVD), according to results from the Long Island Breast Cancer Study Project (LIBCSP).

 found a 17% risk reduction in the age-matched comparison group from the same source population: women without breast cancer but who also had a history of MHT use.

“MHT increases the risk of developing breast cancer through the mechanisms of promoting breast cell proliferation and division. 

These mechanisms are also believed to influence prognosis for breast cancer,” said first author Tengteng Wang, PhD, a research fellow in epidemiology at Harvard University and Brigham and Women’s Hospital in Boston. 

“However, most observational epidemiologic studies conducted among women with breast cancer have reported that prediagnosis MHT is associated with a reduced risk of mortality. Such conflicting results inspired me to further clarify the association between MHT and mortality outcomes, especially among breast cancer survivors.”

The investigators interviewed 1,508 women from LIBSCP who had been newly diagnosed with first primary breast cancer between 1996 and 1997, along with 1,556 age-matched women without breast cancer from LIBSCP. Both groups were asked about MHT usage.

The National Death Index (NDI) provided vital status after a median follow-up of 16 years, during which time there were 915 overall deaths in the two groups combined.

Women with breast cancer who had taken MHT prior to diagnosis were 23% less likely to die overall, 31% less likely to die from breast cancer specifically, and 43% less likely to die from CVD compared with MHT never users.

Differences in breast cancer-specific mortality according to hormone receptor (HR) status were also observed: 56% less risk for negative tumors and 4% less risk for positive tumors in ever vs. never users.

“I was surprised that except for breast cancer mortality, prediagnosis MHT was associated with a strong risk reduction of CVD-specific mortality, because previous studies that investigated the association between prediagnosis MHT and mortality among women with breast cancer did not report CVD mortality as a major outcome,” Dr. Wang told 

“I also found unexpected a more pronounced mortality reduction for breast cancer with hormone receptor-negative tumors than for positive tumors, because prior studies mostly report similar associations of MHT-breast cancer mortality by hormone receptor status.”

The study underscores that for patients with breast cancer who used MHT before diagnosis, MHT may be part of the cause of the breast cancer, but that these patients need not worry that such exposure history may increase their likelihood of dying from breast cancer. 

“This is an important message that directly helps clinicians in counseling women about MHT,” Dr. Wang said.

Although usage of MHT has declined dramatically in recent years, “most older American women currently diagnosed with breast cancer have used MHT at some point in their lifetime,” Dr. Wang said.

Besides women needing to understand the broad health risks and benefits of taking MHT, “the therapy should be given according to Food and Drug Administration (FDA) recommendations, which is at the lowest effective dose and for the shortest duration that is consistent with treatment goals and risks for individual,” Dr. Wang said.

To further clarify the effect of MHT on breast cancer mortality, Dr. Wang advocates future studies that examine the link between MHT and mortality by tumor molecular subtypes, as well as other tumor characteristics of aggressiveness.

Dr. Wang reports no relevant financial disclosures.

Wang T, Bradshaw PT, Moorman PG, et al. Menopausal hormone therapy use and long-term all-cause and cause-specific mortality in the Long Island Breast Cancer Study Project. 

. Published online June 25, 2020. doi:10.1002/ijc.33174

A study from the Long Island Breast Cancer Study Project (LIBCSP) investigated the association between menopausal hormone therapy (MHT) and mortality outcomes among breast cancer survivors.

Menopausal hormone therapy and mortality in breast cancer survivors

This finding was independent of traditional cardiovascular risk factors.

The investigators assessed the connection between a history of breastfeeding and indices of subclinical atherosclerosis in 197 parous postmenopausal women (mean age 55.7 years) with a history of breastfeeding.

All study patients were treated at the Menopause Clinic of the Aretaieio Hospital, University of Athens, Greece.

Subclinical atherosclerosis was diagnosed via pulse wave velocity (PWV), intima-media thickness [IMT] and the presence of atherosclerotic plaque.

Compared to women who reported breastfeeding for only 1 to 5 months, women who reported doing so for at least 6 months had significantly lower values for common carotid artery IMT: model R2 = 15.7%, b-coefficient = -0.170; 95% confidence interval (CI): -0.208 to -0.001 (

Furthermore, after adjusting for traditional risk factors, women with a longer duration of breastfeeding were much less likely to have subclinical atherosclerosis: model X2 = 28.127, odds ratio (OR) = 0.491; 95% CI: 0.318 to 0.999 (

However, the prevalence of plaques in carotid arteries was not linked to breastfeeding: 16.2% among women with longer breastfeeding duration vs. 19.7% for shorter duration (

“The pathophysiological pathways mediating our findings are difficult to be established,” wrote the authors. “Breastfeeding women have higher circulating prolactin, a hormone shown to stimulate maternal beta-cell proliferation in pregnant mice.”

A recent analysis of data from the Nurses’ Health Study found that women with baseline prolactin levels in the highest quartile were less likely to develop diabetes later in life compared to women whose prolactin levels were in the other quartiles.

In addition, oxytocin, “released by the posterior pituitary upon nipple stimulation by the lactating infant, has been shown to lower the reactivity of the autonomous nervous system to stress and therefore regulates blood pressure,” wrote the authors.

Other studies support the benefits of breastfeeding in decreasing the risk for overt cardiovascular disease, including the European Prospective Investigation into Cancer and Nutrition (EPIC), which found that a personal history of breastfeeding was associated with a 29% lower risk of coronary events compared to the risk in women who had never breastfed.

The second Nord-Trøndelag Health Survey (HUNT2) also concluded that women who never breastfed were 2.5 times more likely to experience a fatal cardiovascular event as opposed to women who breastfed for at least 24 months, after adjustment for the number of pregnancies, cardiovascular risk factors and social factors.

Likewise, the Study of Women’s Health Across the Nation (SWAN) found a 5.26-fold higher risk for aortic calcification in women with no personal history of lactation versus women who had breastfed.

The current investigators noted that a longer duration of breastfeeding may have a beneficial effect on subclinical atherosclerosis later in life.

“If this association indicated by the study is causative, the history of breastfeeding could aid as prognostic marker for prediction of future cardiovascular risk,” the authors concluded.

Augoulea A, Armeni E, Paschou SA, et al. Breastfeeding is associated with lower subclinical atherosclerosis in postmenopausal women. 

Postmenopausal women who breastfed for at least 6 months cumulatively have a significantly lower incidence of subclinical atherosclerosis compared to postmenopausal women who breastfeed for a shorter duration, according to a cross-sectional study in the journal Gynecological Endocrinology. 

Subclinical atherosclerosis in postmenopausal women who breastfed

Deviation from treatment guidelines for women undergoing interval debulking surgery for advanced epithelial ovarian cancer resulted in a significantly lower 5-year overall survival (OS) compared with results in those who remained treatment compliant, according to a study in the journal 

“One of the primary treatment strategies for advanced epithelial ovarian cancers includes neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and adjuvant chemotherapy,” wrote the authors from Tata Memorial Hospital in Mumbai, India.

The study comprised 182 women diagnosed with advanced epithelial ovarian cancer (stages IIIC-IV) who underwent IDS at the hospital between October 2012 and September 2013.

The standard chemotherapy regimen included three to four cycles of taxanes and platinum as combination chemotherapy. The chemotherapeutic agents given were paclitaxel 175 mg/m2 and carboplatin at a dose of area under the curve 5‐6 every 3 to 4 weeks.

At the end of the third cycle, chemoresponse in the patients was assessed with clinical examination, assessment of cancer antigen 125 (CA-125) levels, and computed tomography (CT) scans.

Optimal response to chemotherapy was defined as radiological evidence of no or minimal ascites, absence of pleural effusion, a decrease in gross abdominal disease by at least 50% of the initial disease at presentation, and reduction in CA-125 levels.

All patients met these criteria and subsequently underwent IDS.

Optimal cytoreduction was defined as no residual disease (R0) or residual disease < 1 cm (R1) at the completion of surgery. Two to three cycles of adjuvant chemotherapy (platinum and taxane) were then scheduled within 3 to 4 weeks of surgery.

All patients had a clinical examination and CA-125 testing every 3 to 4 months for the first 2 years after surgery, and every 6 months for the next 3 years. Radiological investigations were limited to those in whom disease recurrence was suspected.

At each phase of treatment, the investigators documented treatment deviations, which were characterized as deviations from the above‐mentioned protocol, whether treatment- or patient-related.

During the chemotherapy phases, reasons for protocol deviation were divided into four categories: administration of single-agent chemotherapy instead of two agents; administration of more than four or less than three cycles of chemotherapy; longer than 6 weeks between chemotherapy cycles; and administration of nonplatinum‐ and/or taxane‐based chemotherapy. 

During the IDS phase, a delay of more than 6 weeks for surgery after deciding to perform IDS was considered a deviation.

Likewise, as the number of deviations increased, there was a reduction in the OS: 58.2% for no deviation vs. 11.1% for three deviations (

The most common reason for treatment deviation during all phases of treatment was unknown reason (n = 37), followed by single-agent chemotherapy (29), logistic issues such as lack of beds (20), excessive therapy cycles (18), treatment-related toxicity (10), and non-paclitaxel and carboplatin chemotherapy (8).

Deviation or noncompliance with treatment resulted in significantly reduced 5-year OS compared to compliant patients: 34.4% vs 58.2% (

 = .001). This reduction also retained its significance in multivariate analysis (

improve compliance in low‐ and medium‐resource countries

Shylasree TS, Kattepur AK, Gupta M, et al. Compliance to treatment guidelines and survival in women undergoing interval debulking surgery for advanced epithelial ovarian cancer. 

 (Hoboken). 2020; 3(2) (April):e1217. doi:10.1002/cnr2.1217

The study found that both patient- and treatment-related factors contributed to noncompliance.

Author | Bob Kronemyer

Articles

Progesterone vaginal ring for contraception during lactation

Menopausal hormone therapy and mortality in breast cancer survivors

Subclinical atherosclerosis in postmenopausal women who breastfed

Compliance with treatment guidelines for ovarian cancer debulking surgery