Oral Contraceptives and Neutropenia: A Population-Based Cohort Study

Rosenthal, Yael Shalev; Chodick, G; Rosenthal, Adam; Shalev, Varda; Ram, Hila Shalev; Koren, Gideon

doi:10.1007/s40261-019-00818-0

Cited by 2 publications

(4 citation statements)

References 18 publications

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“…The trend observed in the percentage viability of neutrophils treated with levonorgestrel (18.5 ng/mL, 185 ng/mL, 1850 ng/mL) is similar to that of flunitrazepam and tramadol (Figure 3), and suggested that levonorgestrel could alter the phagocytic activities of neutrophils and also result in neutropenia. This is consistent with the findings of who reported low neutrophil function and inflammatory status of women using oral contraceptives [30] , and that of who observed an increase in the proportion of neutropenic women after initiating oral contraceptives [35] . Neutropenia is the abnormal low count of neutrophils [36] and can be caused by drugs, infections, chemotherapy agents, and autoimmune diseases [37] .…”

Section: Discussionsupporting

confidence: 92%

In vitro cytotoxic and inhibitory effect of tramadol, flunitrazepam and levonogestrel on neutrophils and myeloperoxidase

Oyewo,

Ajayi,

Oso

et al. 2024

Trends Immunother.

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The abuse of flunitrazepam, tramadol and levonorgestrel among adolescents is a major problem, with adverse effects on the immune system. Neutrophils serve as the host primary defense and employ the role of an essential enzyme, myeloperoxidase. This study investigated the in vitro effect of flunitrazepam, tramadol and levonorgestrel on the activity of the neutrophil. Neutrophils were isolated from blood samples of volunteers and seeded in culture plates, and then treated with flunitrazepam, tramadol and levonorgestrel. Trypan blue exclusion assay was used to assess the cytotoxic effect of flunitrazepam, (15, 150, 1500, 15,000, 150,000 ng/mL), tramadol (300, 3000, 30,000 µg/ml) and levonorgestrel (18.5, 185 and 1850 ng/mL) on the neutrophils, and the effect flunitrazepam (150,000 ng/mL), tramadol (30,000 µg/ml) and levonorgestrel (1850 ng/mL) on myeloperoxidase activity was assessed. The viability of neutrophils treated with flunitrazepam, (15,000, 150,000 ng/mL), tramadol (300, 3000, 30,000 µg/ml) and levonorgestrel (18.5, 185 and 1850 ng/mL) decreased significantly (p < 0.05) compared with control. Myeloperoxidase activity in neutrophils treated with flunitrazepam (150,000 ng/mL), tramadol (30,000 µg/ml) and levonorgestrel (1850 ng/mL) decreased significantly (p < 0.05) compared with background and positive control. This study revealed that flunitrazepam, tramadol and levonorgestrel altered the activity of myeloperoxidase and phagocytic activities of the neutrophil.

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Section: Discussionsupporting

confidence: 92%

In vitro cytotoxic and inhibitory effect of tramadol, flunitrazepam and levonogestrel on neutrophils and myeloperoxidase

Oyewo,

Ajayi,

Oso

et al. 2024

Trends Immunother.

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“…Oral aphthous ulcers are a common complaint with an estimated point prevalence of 4% 40 . In our recent study, 3 we described the case that led us to investigate this topic. This patient suffered from recurrent aphthous ulcers throughout her 7-year period of OC use, which resolved after discontinuing OCs.…”

Section: Rrmentioning

confidence: 99%

“…[RR] = 1.2, 95% confidence interval [CI] 1.1-1.35, P < .01). 3 Oestrogen receptors 4 are expressed in various lymphoid tissue cells including lymphocytes, macrophages, and dendritic cells. 5 To date, numerous studies have investigated the relationship between sex hormones and the immune system, demonstrating immunomodulatory effects of oestrogens.…”

Section: Introductionmentioning

confidence: 99%

“…In the USA, 35% of adult women are currently using hormonal methods of contraception and 88% were exposed to some form of contraceptive 2 . In a recent study we have shown that the use of OCs is associated with increased risk of neutropenia (risk ratio [RR] = 1.2, 95% confidence interval [CI] 1.1–1.35, P < .01) 3 Oestrogen receptors 4 . are expressed in various lymphoid tissue cells including lymphocytes, macrophages, and dendritic cells 5 .…”

Section: Introductionmentioning

confidence: 99%

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Association between oral contraceptives and serious infections: A population‐based cohort study

Rosenthal

Ram

et al. 2021

Brit J Clinical Pharma

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Oral contraceptives (OC)s are commonly used worldwide. In a recent study, we showed that the use of OCs is associated with an increased risk for neutropenia. We aimed to investigate the clinical implications of this finding by examining the infection rates of 4 serious infections before, during and after OCs.Methods: A retrospective cohort study using the electronic medical records of a large health organization. We selected 2 retrospective cohorts of women aged 16-40 between years 2005 and 2019. The first cohort examined infection rates during 2 years before OC use and 2 consecutive years of adherent OC use. The second cohort included women who consumed OCs adherently for 2 years and then discontinued their use for 2 consecutive years. Women's infection rates were compared by χ 2 test, results were stratified by OC type and age.Results: Overall, 21 595 and 20 728 women were included in Cohorts 1 and 2 respectively. We found a statistically significant higher relative risk for infection while using OCs; the overall risk ratios (95% confidence intervals) for infection in Cohorts 1 and 2 were 1.35 (1.32-1.38) and 1.27 (1.24-1.31), respectively. The overall infection risk remained statistically significant when stratified by age.Conclusions: This study demonstrates a high statistically and clinically significant risk for all infections followed during OC consumption, which is likely to have major clinical and economic implications. These findings may have implications to millions of women worldwide and should lead to more research on the safety of the pill.

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Oral Contraceptives and Neutropenia: A Population-Based Cohort Study

Cited by 2 publications

References 18 publications

In vitro cytotoxic and inhibitory effect of tramadol, flunitrazepam and levonogestrel on neutrophils and myeloperoxidase

In vitro cytotoxic and inhibitory effect of tramadol, flunitrazepam and levonogestrel on neutrophils and myeloperoxidase

Association between oral contraceptives and serious infections: A population‐based cohort study

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