Renée Bacher

Oral contraceptives (OCs) may have an additional benefit for young athletes: protection from tears in the anterior cruciate ligament (ACL). A 

shows that the rate of ACL tears was 63% lower in women aged 15 to 19 taking the pills than in those not on the contraceptives.

 According to the authors, their findings confirm results from previous studies. The report, by researchers from Brown University, was based on a review of data from The PearlDiver database on OC users aged 15 to 49. Women undergoing surgery for an ACL tear were compared to a control group having the same procedure who were not on OCs. Chi-squared testing was used to assess for significant differences in the rate of ACL reconstruction for the two groups, with age groups broken down into 5-year intervals.

A total of 82,874 patients were studied. Looking at the 15-to-19 age group, the authors found that 29.35% of ACL surgeries were in women not on OCs versus 13.33% in women on OCs. The odds ratio (OR) for ACL reconstruction while on OCs across all age groups was 0.82 (Ï 2 = 0.001, 95% CI 0.72–0.92) compared to not using OCs. In the 15-to-19 age group, the OR was 0.37. The number needed to treat for OC usage in women in that group was six patients.

In previous studies, the likelihood of experiencing an ACL tear was found to be greatest during ovulation, the phase inhibited by OCs. The authors concluded that prescribing OCs to inhibit the elevated levels of estrogen and progesterone during the ovulatory phase can prevent both increased laxity of the ligament and ACL tears. 

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Oral contraceptives (OCs) may have an additional benefit for young athletes.

Could OCs help protect against ACL tears? 

In young women, anorexia nervosa (AN) can lead to fractures because bone mass acquisition is highest in females during puberty and late adolescence. Oral contraceptives (OCs) may partially protect these patients from loss of bone density, according to results of a study published in 

Areal bone mineral density (aBMD) was higher in patients with AN on OCs than those who did not take the contraceptives. And the longer the duration of OC use and shorter the period between AN onset and start of the contraceptives, the greater the aBMD preservation. The researchers also observed that the best bone tissue responses were seen in patients with more severe AN. 

The cross-sectional study, done at the University of Montepellier in France between 2009 and 2016, enrolled 305 women aged 14.5 to 34.9 with AN, 99 of whom were on OCs, and 121 age-matched controls, none of whom were taking medication known to affect bone metabolism. 

Patients’ standing height and body mass index (BMI) were calculated and aBMD was evaluated with dual-energy x-ray absorptiometry and bone turnover markers, with leptin evaluated concomitantly. In the women with AN who were not on OCs, aBMD at whole body and femoral neck was positively and strongly associated with BMI (

< .001, respectively). In the group not on OCs, however, the aBMD for whole body and femoral neck remained stable whatever the BMI (

“It is worth noting that multiple adjustments on these co-variables did not modify the differences between the groups. In addition, the evaluation of OC use in a setting of current medical practice is a strong point of this study because it reinforces the potential utility of this therapy to partially protect bone tissue in young AN patients, who are seen routinely in our clinical practice,” the report said. 

While the authors encourage the prescription of contraceptives to limit bone loss in young patients with AN, particularly in those presenting as extremely underweight, they urge clinicians not to rely solely on this treatment as it does not provide total protection of bone mass. Careful monitoring of bone mass is needed in these patients until new therapeutic approaches are developed. 

Although OCs do not provide total protection of bone mass, they may help limit bone loss in young patients with AN.

OCs may partially avert anorexia-related bone loss

A recent study of the association between rotating night shift schedules and age at menopause suggests a modest acceleration of reproductive senescence in a large national cohort of nurses. The risk may be greater in women under age 45 and in those who work rotating night shifts frequently.

According to the study, published in a recent issue of 

, this is the first prospective investigation of the association of night work with menopausal timing. “Due to the complexity of central reproductive regulation, competing mechanisms support that women working more rotating night shifts over their reproductive lifetime could experience either delayed or advanced menopausal onset,” the authors said.

The cohort study included 80,840 women in Nurses’ Health Study 2 (NHS2) and follow-up was from 1991 to 2013. The participants were registered nurses in the United States aged 25 to 42 when the study began in 1989. Every other year for 22 years they sent in questionnaires that included information on lifestyle, medical conditions and use of medications, as well as other environmental and occupational exposures. 

Women in menopause were excluded as were those who used menopausal hormone therapy or had been diagnosed with cancer (other than non-melanoma skin cancer) on, or prior to returning the 1993 questionnaire. Women were also excluded if they did not return the baseline 1991 questionnaire or had missing or incomplete records for their rotating night shift work exposure at, or before the study baseline.

According to the report, 34% of women studied had reached natural menopause at follow-up. Participants who worked 20 months or more of rotating night shifts in the previous 2 years had an increased risk of earlier menopause (multivariable-adjusted (MV)-HR = 1.09, 95% CI: 1.02–1.16) than those who did not do rotating night shift work. 

The risk was higher in women undergoing menopause or otherwise censored under age 45 (MV-HR = 1.25, 95% CI: 1.08–1.46), than it was for those continuing in the study who were older than age 45 (MV-HR = 1.05, 95% CI: 0.99–1.13). Higher risk of menopause in women who reached menopause before age 45 was associated with working 10 or more years of cumulative rotating night work (MV-HR10–19 years = 1.22, 95% CI: 1.03–1.44; MV-HR  ≥20 years = 1.73, 95% CI: 0.90–3.35), but the association between menopause and night work was not seen in women older than age 45 (MV-HR10–19 years = 1.04, 95% CI: 0.99–1.10; MV-HR ≥ 20 years = 1.01, 95% CI: 0.89–1.15).

The researchers used cox proportional hazards models to estimate hazard ratios for menopause, adjusted for age, smoking status, body mass index, physical activity, alcohol consumption, reproductive factors, and exogenous hormone use.

“So far, we can only speculate the degree to which disruptive circadian stimuli, through cascade effects on central and peripheral HPOA targets, including nocturnal melatonin suppression, may play a role,” the authors said. “Further study of the interplay between circadian signaling and biological mediators of stress among shift workers, in addition to validation of this finding among studies using more detailed shift schedule data, is recommended.” 

Results of the study suggest that women who already may be prone to earlier menopause may further shorten their reproductive years by working rotating night shifts. In addition to reducing a woman’s reproductive life, earlier menopause increases risk of cognitive decline, osteoporosis, cardiovascular disease, and a shorter lifespan. 

Disruptions in circadian stimuli resulting from their work schedule may put nurses under age 45 at higher risk for accelerated onset of menopause. 

Rotating night shift schedules may speed early menopause

Early menopause has long been correlated with cardiovascular disease (CVD) events including stroke and heart attack. A new 

 suggests the converse may also be true; women who have had premenopausal CVDs were twice as likely to go through menopause at an early age.  

“We found women who had a cardiovascular event before age 35 had twice the risk of being in menopause by the time they reached 45,” said Dongshan Zhu, MD, lead author of the 

 and a researcher at the School of Public Health, University of Queensland, Brisbane, Australia. “Women who had them after 40 were more likely to experience a ‘normal’ menopause at around 51.”

Reduced estrogen circulation during menopause can trigger vascular aging, and recent findings suggest menopausal hormone therapy (MHT) may not reduce CVD risk and may even increase it.  “This inconsistency led us to consider the converse model, i.e., that cardiovascular damage itself is a driving factor in the process of ovarian aging,” the report said. “This model is indirectly supported by two studies. In the 

, Kok et al. found that premenopausal cardiovascular risk factors were associated with younger age at menopause. 

 reported that women who experienced early natural menopause were more often smokers, had diabetes, and had higher average body mass index (BMI). CVD risk factors are associated with women’s age at natural menopause and the question that follows is whether premenopausal CVD events might also be linked to reproductive aging and early age at natural menopause. To date, no study has examined this question directly.” 

The authors used information from nine studies in the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE) to look at the association between premenopausal CVD events and age at natural menopause. Data collection in the studies was both retrospective and prospective, with CVD events ascertained by self-report and/or hospital diagnosis. 

The analysis represents data from 177,750 women who answered yes or no to questions about pre-or postmenopausal CVD events as well as giving their age at onset of an event and at natural menopause. The researchers made adjustments in the data from the self-reported surveys for confounding factors such as race/ethnicity, BMI, education, hypertension, smoking, and family history of CVD. 

According to the report, the researchers used multinomial logistic regression models to estimate multivariable relative risk ratios (RRR) and 95% confidence intervals (CI) for associations between age at onset of premenopausal CVD events-including coronary heart disease (CHD) and stroke-and age at natural menopause. 

Altogether 1561 (0.9%) premenopausal participants reported CVD events (including 1130 CHD and 469 stroke) at a mean age of 41.3 years. Risk of menopause before age 45 was twofold higher in women who experienced a first CVD event before age 35 than in those with no history of a premenopausal CVD event (adjusted RRR [95% CI] 1.92 [1.17-3.14] for any CVD, 1.86 [1.01-3.43] for CHD and 2.17 [1.43-3.30] for stroke). For 47% of premenopausal CVD events reported by patients, no validation was available in hospital records.

According to Dr. Zhu, these findings should send a strong message to doctors of young women with heart disease. “These women should be alerted by their physicians for their future high possibility of having early menopause, because early menopause is associated with higher risk of death, Type 2 diabetes and osteoporosis,” he said, adding that because most of the women in the study were white, more research is needed to see whether the findings hold true for women of other races and ethnic groups.

The timing of a woman's cardiovascular event may play a prominent role in her menopause onset.

Premenopausal CVD may mean menopause at an early age

Hysteroscopy is significantly more accurate than transvaginal ultrasonography (TVUS) for diagnosing endometrial polyps in postmenopausal women than in premenopausal women, according to new research by Israeli investigators. The findings, the authors said, may be useful in counseling patients. 

Results of the retrospective study, conducted at two tertiary medical centers in Israel, were published in the 

Journal of Obstetrics and Gynaecology Canada

The authors reviewed records from 2010 to 2014 from 694 women who had a suspected endometrial polyp diagnosed with TVUS and then underwent hysteroscopy to more fully visualize the entire uterine cavity. The study included TVUS performed in different locations and by different health care providers. The average age of patients was 49 and the majority of the premenopausal patients included had abnormal uterine bleeding (AUB), which can complicate timing of the procedure. 

The patients were divided into two groups, one premenopausal (395 patients) and the other postmenopausal (299 patients), and compared.  Hysteroscopy confirmed the TVUS diagnosis in 212 (71%) postmenopausal patients versus 212 (53%) premenopausal patients (

< 0.001). Of the excised polyps observed by hysteroscopy, 95% were confirmed with histology in the postmenopausal patients, versus 85% in the premenopausal patients (

In postmenopausal women, the size of an endometrial polyp did not change the accuracy of TVUS diagnosis. However, in premenopausal women whose polyps were smaller than 10 mm, the procedure was significantly less accurate (

AUB was the most common presenting symptom in the premenopausal patients (69%), whereas the majority of the postmenopausal women (61%) were asymptomatic. 

Endometrial polyps can be caused by estrogen-related factors in premenopause and perimenopause or by non−estrogen-related factors that are not completely understood. Therefore, risk of malignancy and optional monitoring and treatment are different in the two patient populations. 

Although TVUS is considered the first choice for diagnosis of uterine cavity disorders, some doctors and researchers question use of it to screen for endometrial disease in patients without symptoms. Treatment of asymptomatic polyps, the authors noted, is controversial, because early diagnosis of asymptomatic endometrial cancer has not been proven to increase survival rates.  

The researchers found that in women with abnormal bleeding especially, the most appropriate time for TVUS and hysteroscopy to be scheduled is before menopause, as this is when the diagnostic value for polyps is at its highest. Limitations of the study they noted were the retrospective design, use of two-dimensional TVUS, and difficulty associated with timing of TVUS and hysteroscopy in the premenopausal patients who had AUB. 

Researchers in Israel looked at the effectiveness of hysteroscopy compared with TVUS in diagnosing polyps in postmenopausal women.

Menopausal status and endometrial polyp diagnosis

A recent prospective cohort study in France has found no strong influence of menopausal hormone therapy (MHT) use on risk of cutaneous melanoma. The results are in contrast to findings from previous studies and conclusions from a 2011 meta-analysis. 

Etude Epidemiologique auprÃ¨s de femmes de l’Education Nationale, or E3N, was a prospective cohort of 98,995 French women who were aged 40 to 65 in 1990. The aim was to assess associations between MHT use and melanoma risk in a population with access to a wide variety of MHT formulas. That diversity allowed researchers to analyze formulations of estrogen therapy (ET) that aren’t often found in other countries and its findings suggest that social and behavioral factors have a role in the relation between melanoma risk and MHT use.  

The researchers assessed MHT use through questionnaires that were self-administered every other year, using Cox proportional hazards regression models to adjust for age and skin cancer risk factors. 

From 1990 to 2008, there were 444 melanoma cases among 75,523 postmenopausal women. MHT use was associated with a higher melanoma risk (hazard ratio [HR]=1.35, 95% confidence intervals [CI]=1.07-1.71). 

Past users were at the highest risk for melanoma (HR=1.55, CI=1.17-2.07, homogeneity for past vs. recent use: 

= 0.11), as were those who used MHT containing norpregnane derivatives (HR=1.59, CI=1.11-2.27), but there was no heterogeneity across types of MHT (

= 0.13). MHTs were classified as: 1) estrogen only (systemic estradiol, conjugated equine estrogens [CEE], or unknown oral estrogens); 2) estrogen combined with a progestogen or an androgen; 3) low potency or “weak” estrogens (promestriene or estriol); or 4) tibolone, other, or unknown. The researchers also distinguished among combined therapies: micronized progesterone, dydrogesterone, pregnane derivatives (chlormadinone acetate, cyproterone acetate, medroxyprogesterone acetate [MPA], medrogestone), nopregnane derivatives (promegestone, demegestone, nomegestrol acetate), and testosterone derivatives. ET was considered as oral, trans-cutaneous, and other or unknown.

Duration of us did not impact melanoma risk, but a higher risk was observed when treatment onset occurred shortly after menopause (< 6 months: HR=1.55, CI=1.16-2.07 vs. ≥ 2 years). 

After adjustment for ultraviolet (UV) exposure, associations between MHT use and melanoma risk were similar, but women taking MHT were more likely to report using sunscreen than those who did not use the drugs. 

“A surprising finding in our research was the higher risk of melanoma observed among MHT users when therapy onset was close to menopause,” said Marie-Christine Boutron-Ruault, MD, PhD, a co-author of the study. “This pattern was also observed for combined therapies and breast cancer, although there are no clear mechanistic explanations for this pattern to date.”

In the literature, data on breast cancer, the major hormone-dependent cancer in women, show that risk of breast cancer increases linearly with duration of use, and decreases after cessation of use. “Such associations were not found with cutaneous melanoma in our study,” Dr. Boutron-Ruault said.

According to the authors, further investigation is needed to explore potential effect modification by UV exposure in women using MHT. Dr. Boutron-Ruault added that research including social and behavioral descriptions of MHT users is needed to understand the mechanisms underlying the association observed between MHT use and melanoma risk in epidemiologic studies. 

In particular, she said, further investigation is needed into whether this association is related to the involvement of steroid hormones in the biology of melanoma, or to the physical and behavioral profiles of MHT users. 

The research team recently found a modest positive association between oral contraceptive use and melanoma risk, notably for long durations of use, and a study is under way to explore whether cumulative use of exogenous hormones could influence melanoma risk.

“Although firm conclusions cannot be drawn from our data, socioeconomic factors, notably sun exposure behaviors, could partially explain the associations observed between MHT and melanoma risk,” said Dr. Marie-Christine Boutron-Ruault.

New results from a prospective cohort study conflict with finding from previous studies regarding MHT and cutaneous melanoma risk.