Combined Hormonal Contraceptive Users Research Articles

Hormone-related side effects in new users of a levonorgestrel 52-mg intrauterine device

Although the levonorgestrel 52 mg intrauterine device is locally active and has low systemic hormone exposure, hormonal intrauterine device users sometimes report hormone-related side effects. Evaluate hormone-related adverse event rates among all participants and compare these among those who used combined hormonal or no hormonal contraception in the month before enrollment. A total of 1714 women aged 16-45 years old received a levonorgestrel 52 mg intrauterine device in a multicenter phase 3 trial to evaluate contraceptive efficacy and safety for up to 10 years. This analysis evaluated a subset of participants who used combined hormonal or no hormonal contraception in the month prior to device placement. We assessed all non-expulsion, non-bleeding-related events with ≥1% incidence at 180 days with a plan to include weight increase regardless of incidence; we excluded events considered non-hormonal. We computed 180-day side effect frequency rates based on the number of days a side effect was reported during the study period. We created a multivariable model for side effect incidence at 180 days based on age, race, ethnicity, body mass index at enrollment, parity, and contraception use in the month before enrollment. For those side effects with a p-value <0.2 on univariate comparison between combined-hormonal and no-hormonal contraception users, we secondarily evaluated 360-day event rates. Overall, 644 participants used combined hormonal contraception (primarily oral [n=499, 77.5%]) and 855 used no hormonal method before IUD placement. Individual side effect rates over the first 180 days did not differ between prior combined-hormonal and no-hormonal contraception users except for acne (84 [13.0%] versus 73 [8.5%], respectively), p=0.006, OR 1.61 (95% CI 1.15-2.24). However, this association was weaker after adjustment for age, race, ethnicity, obesity status, and parity (aOR 1.40, 95% CI 0.99-1.98) At 360 days, prior combined hormonal contraception users were more likely to report acne (101 [15.7%] vs. 91 [10.6%], respectively, p=0.005) and orgasm/libido problems (20 [3.1%] vs. 12 [1.4%], respectively, p=0.03). Over the first 180 days, all side effects other than acne were reported in less than 3% of days; acne was reported an average of 13 days (7.4%) per prior combined hormonal contraception user and 9 days (5.0%) per prior non-hormonal contraception user (p<0.0001). Discontinuation for evaluated side effects occurred in 83 (5.5%) participants with no difference between those who used combined hormonal (36 [5.6%]) or no hormonal contraception (47 [5.5%]), p=1.0) before study entry. Using combined hormonal contraception prior to levonorgestrel 52 mg intrauterine device placement is only weakly associated with reporting hormonally related side effects like acne. Only a small percentage of levonorgestrel 52 mg intrauterine device users experienced potentially hormone-related side effects during the initial 6 months of use that resulted in discontinuation.

Quality of life of patients with uterine fibroids

BACKGROUND: Currently, there is an elevation in the incidence of uterine fibroids in increasingly younger women of reproductive age. Taking into account the current trend of late motherhood, this cohort of patients is interested in using reliable reversible contraception. Combined hormonal contraceptives meet these criteria and are able to neutralize the clinical manifestations of uterine fibroids, thereby improving the quality of life of patients. At the same time, some combined hormonal contraceptives users may experience a decrease in libido and a change in their psycho-emotional state as a manifestation of the side effects of these drugs. AIM: The aim of this study was to assess the effect of combined hormonal contraceptives on the quality of life in patients with uterine fibroids. MATERIALS AND METHODS: This study involved 100 patients with uterine fibroids (F3–F6 according to classification of the International Federation of Gynecology and Obstetrics, without indications for surgical treatment) and 30 healthy women aged 18 to 49 years. For contraceptive purposes, 40 participants with uterine fibroids used combined hormonal contraceptives containing ethinyl estradiol (group I) and 60 patients with uterine fibroids did not use any medications (group II). The following validated questionnaires were used for patients with uterine fibroids — at the beginning and after 6 months, and for healthy women in the control group (group III) — once upon entry into the study: Short Form-36, Female Sexual Function Index, and Beck Depression Inventory. A comparative statistical analysis of the studied parameters over time was carried out. RESULTS: At baseline, a lower quality of life was noted in patients with uterine fibroids compared to the control group (Short Form-36): 94 ± 6 vs 102 ± 11 points, respectively (p 0.05). After 6 months, patients in group I showed positive dynamics with increasing in the total Short Form-36 from 95 ± 4 to 98 ± 5 points (p 0.05) compared to patients in group II: 94 ± 6 and 93 ± 5 points (p 0.05). We revealed no changes in the Female Sexual Function Index in the study groups — at baseline: 24.8 ± 8.9 (group I), 23.9 ± 9.5 (group II), and 27.8 ± 4.7 (group III); and after 6 months: 26.4 ± 9.2 (group I) and 23.9 ± 10.0 (group II) (p 0.05 for all comparisons). When comparing the results of a questionnaire on the Beck scale, no dynamics were determined in patients with uterine fibroids, including those who used combined hormonal contraceptives. CONCLUSIONS: The study demonstrated a lower quality of life in patients with uterine fibroids compared to healthy women and an improved quality of life in patients with uterine fibroids using combined hormonal contraceptives. We showed no negative effects of contraceptive drugs on libido and emotional state in women with uterine fibroids who used combined hormonal contraceptives for 6 months.

Longitudinal profile of estrogen-related thrombotic biomarkers after cessation of combined hormonal contraceptives

AbstractThe persistence of risk of venous thromboembolism (VTE) due to combined hormonal contraceptives (CHCs), after their cessation, is unknown but important to guide clinical practice. The objective of this prospective cohort study was to define the time until normalization of estrogen-related thrombotic biomarkers after CHC cessation. We enrolled women aged 18 to 50 years who had decided to stop their CHC, excluding those with a personal history of VTE, anticoagulation, or pregnancy. The study started before cessation of CHC, with 6 visits afterwards (at 1, 2, 4, 6, and 12 weeks after cessation). Primary outcomes were normalized sensitivity ratios to activated protein C (nAPCsr) and to thrombomodulin (nTMsr), with sex hormone–binding globulin (SHBG) as a secondary end point. We also included control women without CHC. Among 66 CHC users, from baseline until 12 weeks, average levels of nAPCsr, nTMsr, and SHBG decreased from 4.11 (standard deviation [SD], 2.06), 2.53 (SD, 1.03), and 167 nmol/L (SD, 103) to 1.27 (SD, 0.82), 1.11 (SD, 0.58), and 55.4 nmol/L (SD, 26.7), respectively. On a relative scale, 85.8%, 81.3%, and 76.2% of the decrease from baseline until 12 weeks was achieved at 2 weeks and 86.7%, 85.5%, and 87.8% at 4 weeks after CHC cessation, respectively. Levels were not meaningfully modified throughout the study period among 28 control women. In conclusion, CHC cessation is followed by a rapid decrease in estrogen-related thrombotic biomarkers. Two to 4 weeks of cessation before planned major surgery or withdrawal of anticoagulants in patients with VTE appears sufficient for the majority of women. The trial is registered at www.clinicaltrials.gov as #NCT03949985.

Comparison of thromboembolism outcomes in patients with sickle cell disease prescribed hormonal contraception

AbstractPatients with sickle cell disease (SCD) are at a risk of thromboembolism (TE), and use of hormonal contraception can further increase that risk. This study aims to assess patterns of hormonal contraceptive use and compare risk of contraception-related TE between combined hormonal contraceptives (CHCs) and progestin-only contraceptives (POCs). Patients with SCD aged between 12 and 44 years with a new prescription of a hormonal contraceptive in the Centers for Medicare and Medicaid Services Medicaid Analytic eXtract database (2006-2018) were followed up to 1 year. We identified 7173 new users: 44.6% initiated CHC and 55.4% initiated POC. Combined oral contraceptive pills (OCPs; 36.5%) and progestin-only depot medroxyprogesterone acetate (33.9%) were the most frequently prescribed agents. A total of 1.8% of contraception users had a new diagnosis of TE within 1 year of the first identified contraception prescription. There were no significant differences in TE event rates between CHC and POC users (17.2 and 24.7 events per 1000 person-years, respectively). In patients prescribed OCP, there were no differences in TE event rates based on estrogen dose or progestin generation. Transdermal patch had a 2.4-fold increased risk of TE as compared with that of OCP. Although limited by the retrospective study design and use of administrative claims data, this study found no significant differences in TE rates between new users of CHC and POC in patients with SCD. Careful evaluation of underlying TE risk factors should be considered for each patient with SCD before initiation of hormonal contraception.

Former long-term use of combined hormonal contraception and glucose metabolism disorders in perimenopausal women: A prospective, population-based cohort study.

Current use of combined hormonal contraceptives worsens glucose tolerance and increases the risk of type 2 diabetes mellitus at late fertile age, but the impact of their former use on the risk of glucose metabolism disorders is still controversial. This was a prospective, longitudinal birth cohort study with long-term follow-up consisting of 5889 women. The cohort population has been followed at birth, and at ages of 1, 14, 31 and 46. In total, 3280 (55.7%) women were clinically examined and 2780 also underwent a 2-h oral glucose tolerance test at age 46. Glucose metabolism indices were analyzed in former combined hormonal contraceptive users (n = 1371) and former progestin-only contraceptive users (n = 52) and in women with no history of hormonal contraceptive use (n = 253). Compared with women with no history of hormonal contraceptive use, those who formerly used combined hormonal contraceptives for over 10 years had an increased risk of prediabetes (odds ratio [OR] 3.9, 95% confidence interval [CI]: 1.6-9.2) but not of type 2 diabetes mellitus. Former progestin-only contraceptive use was not associated with any glucose metabolism disorders. The results persisted after adjusting for socioeconomic status, smoking, alcohol consumption, parity, body mass index and use of cholesterol-lowering medication. Former long-term use of combined hormonal contraceptives was associated with a significantly increased risk of prediabetes in perimenopausal women, which potentially indicates a need of screening for glucose metabolism disorders in these women.

Risk of thromboembolism in patients with COVID-19 who are using hormonal contraception.

Risk of thromboembolism in patients with COVID-19 who are using hormonal contraception.

Women’s attitudes about combined hormonal contraception (CHC) - induced menstrual bleeding changes - influence of personality traits in an Italian clinical sample

Objectives We investigated the attitudes to change the frequency of menstrual bleeding by using combined hormonal contraception (CHC). Personality characteristics were also explored. Methods We conducted a cross-sectional study in two university hospitals in northern Italy. Current, past and never CHC users (n = 545; age 18–44 years) completed a self-administered semi-structured questionnaire and the Ten-Item Personality Inventory (TIPI). Results Forty-five percent of responders (n = 301) would prefer to change their bleeding frequency by using CHC. A flexible regimen was the preferred choice (n = 80; 33%) followed by extended regimens to bleed every 3 months (n = 54; 22%) or to never bleed (n = 43; 18%). The main positive reasons were to avoid dysmenorrhea (43%) and have more freedom in sexual (36%) and active (35%) life, whereas the main reason for a negative attitude was ‘menstrual rhythm is natural’ (59%). Age had a significant influence on women’s willingness to change menstrual frequency by using CHC [>39 years (57%), 30–39 years (31%) and <30 years (46%)] (χ2: 9.1; p = 0.01). Never users significantly reported a more negative attitude (71%) in comparison with past (51%) and current users (49%) (χ2: 18.7; p = 0.001). Personality traits played a role, with higher scores of openness (p = 0.005) and extraversion (p = 0.001) in women with a positive attitude. Conclusions Almost half of our study sample reported a preference for changing their menstrual pattern by using CHC. Flexibility was the preferred choice across age and use of CHC. Personality characteristics (openness and extroversion) might influence attitudes toward CHC-induced menstrual bleeding changes.

Risk of thromboembolism in patients with COVID-19 who are using hormonal contraception: a Cochrane systematic review

BackgroundThe coronavirus disease COVID-19 is associated with an increased risk of thrombotic events. Individuals with COVID-19 using hormonal contraception could be at additional risk for thromboembolism, but evidence is sparse.MethodsWe...

Use of combined hormonal contraception and stroke: A case-control study of the impact of migraine type and estrogen dose on ischemic stroke risk.

To clarify how factors such as estrogen dose and migraine history (including migraine subtype) impact ischemic stroke risks associated with combined hormonal contraceptive (CHC) use. CHC use in those with migraine with aura has been restricted due to concerns about stroke risk. We conducted a case-control analysis of stroke risk associated with estrogen dose and migraine history among CHC users in a large tertiary care center. All women aged 18-55 who used a CHC between January 1, 2010, and December 31, 2019, were identified. Those with a stroke diagnosis were identified using ICD codes and confirmed via chart and imaging review. Details of personal and family medical history, stroke evaluation, ethinyl estradiol dosing (EE; ≥30 vs. <30 μg), and demographics were collected. From a random sample of 20,000 CHC users without stroke, a control cohort (n=635) was identified and matched based on patient characteristics, medical and family histories, as well as stroke risk factors, to assess association between migraine diagnosis, migraine subtype, estrogen dose, and stroke. Of the 203,853 CHC users in our cohort, 127 had confirmed stroke (0.06%; CI 0.05%, 0.07%). In unadjusted analyses, a higher number of patients in the case cohort had a diagnosis of migraine (34/127, 26.8%) compared to controls (109/635, 17.2%; p=0.011). Stroke risk was higher with ≥30-μg EE doses compared to those using a <30-μg dose (OR, 1.52; CI 1.02, 2.26; p=0.040). Compared to no migraine, personal history of migraine increased the odds of stroke (OR, 2.00; CI 1.27, 3.17; p=0.003). Compared to no migraine, stroke risk was not significantly increased in those with migraine with aura, but migraine without aura increased the risk (OR, 2.35; CI 1.32, 4.2; p=0.004). Overall stroke risk in our cohort of CHC users was low. When CHCs are used in those with migraine, formulations containing ≤30 μg EE are preferred. Shared decision-making should include discussions about ischemic stroke risks in patients with migraine, even those without aura.

Risk of thromboembolism in patients with COVID-19 who are using hormonal contraception.

Risk of thromboembolism in patients with COVID-19 who are using hormonal contraception.

ASSOCIATION BETWEEN CARDIOVASCULAR RISK FACTORS, ULTRA-SENSITIVE C-REACTIVE PROTEIN, AND FLOW-MEDIATED DILATION OF THE BRACHIAL ARTERY IN PATIENTS USING COMBINED HORMONAL CONTRACEPTIVES: A CROSS-SECTIONAL STUDY

BACKGROUND: Oral combined hormonal contraceptives (CHCs) are one of the most used contraceptive methods worldwide, however, their use may have accessory effects that can generate metabolic, inflammatory, and vascular alterations.OBJECTIVE: To evaluate the association of cardiovascular risk factors, Ultra-sensitive C-reactive protein (US-CRP), and brachial artery flow-mediated dilation in patients using hormonal contraceptives.DESING AND SETTING: This was a cross-sectional study including 109 women (18 to 40 years old) conducted between August 2017 and January 2020 who were assisted at the Brazilian Public Health System in countryside city in northeastern of Brazil.METHODS: The volunteers were divided into two groups according to the use of CHCs and submitted to measurement evaluations of clinical, laboratory, and flow-mediated dilation (FMD) of the brachial artery parameters. RESULTS: The statistical analysis of results between groups showed the following results as total cholesterol (P = &lt; 0.01), high-density lipoprotein, HDL (P = 0.01), triglycerides, TG (P &lt; 0.01), and US-CRP (P = &lt; 0.01). The FMD measurement showed changes in 37.75% (n = 20) of women who were not using CHCs and in 32.15% (n = 18) of women using CHCs (P = 0.37) (odds ratio, OR = 0.78). There were no significant changes between glycemic indexes and parameters clinicals.CONCLUSION: Users of CHCs showed higher levels of total cholesterol, HDL, and triglycerides compared to those who did not use it. The US-CRP results showed a significant increase among CHCs users, however, no change between the FMD values was observed.

Hormonal Contraceptive Use and Association with Thromboembolism in Women with Sickle Cell Disease

Introduction Women with sickle cell disease (SCD) require broad access to highly effective contraceptive methods due to high rates of unplanned pregnancy and adverse maternal and fetal outcomes. Combined (estrogen-containing) hormonal contraception carries a known risk of thromboembolism (TE) in the general population, and women with SCD have higher baseline risk of TE, thus use of these agents in women with SCD may further increase that risk. The paucity of safety data on hormonal contraceptive use in women with SCD limits the ability of providers and patients to make informed decisions. Objectives This study aims to use population-level administrative claims data of publicly insured women with SCD in the United States (US) to assess patterns of hormonal contraception use and evaluate risk of TE during the first year of use. We hypothesized that TE rates are higher in women prescribed combined hormonal contraceptives (CHC) as compared to women prescribed progestin-only contraceptives (POC). Methods We obtained data using the Centers for Medicare and Medicaid Services Analytic eXtract (CMS MAX) from 2006-2018. Study population included females of reproductive age (12-44 years) with >3 ICD-9 or ICD-10 codes consistent with SCD. Women had to have ≥12 months of continuous enrollment with at least 6 months of data as 'washout period' prior to enrollment period. A new prescription for hormonal contraception was identified using national drug codes in pharmaceutical claims or ICD-9 or 10 procedure codes. CHC included the combined oral contraceptive pill (OCP), transdermal patch, and vaginal ring. POC included the progestin-only pill, depot medroxyprogesterone acetate (DMPA) injection, intrauterine device (IUD) and subdermal implant. TE was defined as the presence of ≥2 ICD-9 or ICD-10 codes for venous TE (deep vein thrombosis (DVT) or pulmonary embolism (PE)) or arterial TE (stroke or myocardial infarction (MI)). Arterial TE was also required to have an associated inpatient admission. Women were included in the analysis for 12 months after contraception initiation, or censored in the event of either contraceptive switch, pregnancy or abortion, or TE occurrence. Data were summarized descriptively and TE incidence rates were calculated as events per 1,000 person-years. Results We identified a total of 41,012 reproductive-aged women with SCD enrolled in CMS MAX, of whom 22.6% (n=9,261) had received ≥1 new prescription for hormonal contraception. Among women with new contraceptive use, 58.5% (n=5,420) initiated CHC and 41.5% (n=3,841) initiated POC. Median age at the start of contraception was 22.3 years (range: 12.0-43.9) and median age at the start of CHC and POC were 22.1 and 22.7 years respectively. Among CHC users, 84.6% (n=4,584) of women were prescribed the combined OCP, 7.7% (n=419) the transdermal patch, and 7.7% (n=417) the vaginal ring. For POC users, DMPA was prescribed to 72.3% (n=2,777), progestin-only pills to 21.2% (n=816), IUD to 4.2% (n=163) and subdermal implant to 2.2% (n=85) of women. A total of 141 (1.5%) new contraceptive users with SCD were identified to have a TE during the follow-up period. The median time from contraception initiation to TE diagnosis was 183 days (IQR: 82-244). The most common TE event was PE (46.1%) followed by DVT (41.8%), stroke (6.4%), and MI (2.1%); 3.5% of women had multiple TE events. TE rate was 16.4 events per 1,000 person-years in CHC users, and the TE event rate was 17.0 events per 1,000 person-years in POC users (p=0.84). Rates of TE did not differ between the two most commonly used methods in each group, the combined OCP (15.5 events per 1,000 person-years ) and DMPA (17.7 events per 1,000 person-years) (p=0.48). Conclusion Our work provides population-level data regarding contraceptive practices for women with SCD in the US. We found that CHC was more frequently prescribed than POC, and identified low rates of long-acting reversible contraception use. The most frequently prescribed agents were the combined OCP and the DMPA injection. TE rates after initiation of the combined OCP and DMPA did not differ. Although limited by the retrospective study design and use of administrative claims data, this study suggests a similar safety profile for CHC and POC in women with SCD with respect to risk of TE.

Society of Family Planning Clinical Recommendations: Contraceptive Care in the Context of Pandemic Response

The coronavirus disease 2019 (COVID-19) pandemic has posed a burden to healthcare systems around the world and has changed the way people access health services, including contraception. This document sets forth guidance from the Society of Family Planning for providing contraceptive care in the context of the COVID-19 pandemic, including when access to healthcare is restricted due to pandemic response. It also outlines the role of telehealth for providing contraceptive care beyond the pandemic. Clinicians can use synchronous telemedicine visits and other forms of telehealth to provide many aspects of contraceptive care. Both audio-video and audio-only visits are acceptable forms of telemedicine. Access to permanent contraception should be maintained, especially in the postpartum period. Combined hormonal contraceptive (CHC) users who have asymptomatic or mild COVID-19 infection may continue their contraceptive method, while those admitted to the hospital with severe infection should suspend CHC use until they are clinically recovered. CHC users who take Paxlovid for mild-moderate COVID-19 infection can consider a back-up contraceptive method for the duration of therapy, but clinically relevant drug interactions are unlikely. Future research should examine contraceptive outcomes in people who receive care via telemedicine; and access to telemedicine among historically excluded populations such as adolescents, people of color, people of low socioeconomic status, disabled people, or people who do not speak English as a primary language.

Trends in the use of hormonal contraception in Estonia 2005–2019 and the risk of arterial and venous thromboembolism: a population-based study

Purpose To describe trends in hormonal contraceptive use, incidence of thromboembolism and presence of risk factors for thromboembolism among the users in Estonia. Material and methods Data of 223 312 female patients aged 15–49 years in 2005–2019 from national health insurance databases was derived. Annual prevalence rates of hormonal contraceptive users, incidence rates of thromboembolism and prevalence rates of risk factors were calculated. Results Between 2005–2019 usage of progestogen-only contraceptives (POCs) increased steadily (from 24 to 135 users per 1000 population), whereas combined hormonal contraceptive (CHC) use declined (from 209 in 2012 to 161 users per 1000 population in 2019). During the study period, 390 cases of venous thromboembolism and 108 arterial thromboembolism coincided with hormonal contraceptive use. Incidence rate for venous thromboembolism was 5.0 (95% CI 4.5–5.5) and for arterial thromboembolism 1.4 per 10 000 person-years (95% CI 1.1–1.7) among hormonal contraceptive users. Age adjusted incidence of venous thromboembolism among CHC users was 5.8 (95% CI 4.1–8.2) times higher than in POC users. Among CHC users, 10.3% had more than one risk factor for thrombosis. Conclusions In regards to the risk of thromboembolism, wider use of POCs and declining prevalence of CHCs in Estonia is positive trend. Still, women with history of thrombosis receiving CHC is a serious concern.

Managing the side effects of contraception

Side effects are the most common reason for the discontinuation of contraceptive methods. Dr Katie Boog summarises the available evidence on how to manage them Although often transient, side effects are the most common reason for individuals to discontinue contraception. The evidence to prove causality is limited, as is evidence-based guidance on how to manage these side effects. This article summarises the available evidence. For individuals who have new or worsening acne on progestogen-only contraception (POC), switching to combined hormonal contraception (CHC) is likely to improve their skin. Continuous or extended CHC use may be beneficial for individuals with premenstrual mood change, and for those who experience headaches in the hormone-free interval. Unpredictable bleeding patterns on POC are common. Injectable users can try reducing the interval between injections to 10 weeks. Implant, injectable or intrauterine system users can be offered a 3-month trial of a combined oral contraceptive pill (COC). CHC and POP users with unpredictable bleeding may benefit from switching to an alternative preparation.

Managing the side effects of contraception

Although often transient, side effects are the most common reason for individuals to discontinue contraception. The evidence to prove causality is limited, as is evidence-based guidance on how to manage these side effects. This article summarises the available evidence. For individuals who have new or worsening acne on progestogen-only contraception (POC), switching to combined hormonal contraception (CHC) is likely to improve their skin. Continuous or extended CHC use may be beneficial for individuals with premenstrual mood change, and for those who experience headaches in the hormone-free interval. Unpredictable bleeding patterns on POC are common. Injectable users can try reducing the interval between injections to 10 weeks. Implant, injectable or Intrauterine system users can be offered a 3-month trial of a combined oral contraceptive pill (COC). CHC and POP users with unpredictable bleeding may benefit from switching to an alternative preparation.

Clinical features of migraine with onset prior to or during start of combined hormonal contraception: a prospective cohort study

Many studies have described the features of menstrually related migraines but there is a lack of knowledge regarding the features of migraine in combined hormonal contraceptive users (CHC). Hormone-withdrawal migraines in the pill-free period could differ from those in the natural cycle. Gynaecologic comorbidities, like dysmenorrhea and endometriosis, but also depression or a family history might modify the course of migraine. A better understanding of migraine features linked to special hormonal situations could improve treatment. For this prospective cohort study, we conducted telephone interviews with women using a CHC and reporting withdrawal migraine to collect information on migraine frequency, intensity, triggers, symptoms, pain medication, gynaecologic history and comorbidities (n = 48). A subset of women agreed to also document their migraines in prospective diaries. The mean number of migraine days per cycle was 4.2 (± 2.7). Around 50% of these migraines occurred during the hormone-free interval. Migraine frequency was significantly higher in women who suffered from migraine before CHC start (5.0 ± 3.1) (n = 22) in comparison to those with migraine onset after CHC start (3.5 ± 2.1) (n = 26). Menstrually related attacks were described as more painful (57.5%), especially in women with migraine onset before CHC use (72%) (p < 0.02). Comorbidities were rare, except dysmenorrhea. The majority of migraine attacks in CHC users occur during the hormone-free interval. Similar as in the natural cycle, hormone-withdrawal migraines in CHC users are very intense and the response to acute medication is less good, especially in those women, who developed migraine before CHC use.

26. Venous Thromboembolism Among Concurrent Users of Combined Hormonal Contraceptive and Antifibrinolytics in Adolescents with Heavy Menstrual Bleeding

<h3>Background</h3> Causes for heavy menstrual bleeding (HMB) vary from anovulatory cycles to a bleeding disorder. Treatments for HMB include hormonal and non-hormonal options. Frequently, combined hormonal contraceptives (CHC) are utilized first to control HMB. Venous thromboembolism (VTE) is a rare complication associated with the use of CHC. In adolescents with HMB refractory to CHC, antifibrinolytics (AF) may be used as adjunctive treatment. Concurrent use of CHC+AF theoretically increases risk of VTE, although no current studies have investigated this. The primary objective of this study was to investigate whether concurrent use of AF+CHC to treat HMB in adolescents results in increased VTE. <h3>Methods</h3> IRB approval was obtained to conduct this retrospective chart review at a single institution. ICD10 codes were utilized to identify patients <21 years of age with a diagnosis of HMB. Pharmacy data were utilized to identify those who had medication prescriptions for any CHC and/or AF. Basic demographics were recorded, along with medical history, CHC and AF prescribed. Primary endpoints assessed VTE complications from use of CHC and/or AF. Descriptive statistics were utilized, along with T-Tests. <h3>Results</h3> Chart review identified 2130 HMB patients using CHC and/or AF between 1/2010-12/2019. 470 used AF, 1669 CHC and 91 used both concurrently. The mean age (years) in each group was 18.9 ± 3.1 years (AF), 19.4 ± 3.0 years (CHC), and 19.3 ± 3.0 years (AF+CHC) respectively. The population was diverse. Of 2130 patients, 108 had hyperlipidemia. Mean BMI of AF or CHC users was 24.9, 9% had a personal/family history of bleeding disorder, and 3.8% reported a family history of unprovoked VTE in first/second generation relative. Mean time on therapy was 984 days (CHC), 132 days (AF), and 117 days (CHC+AF). Of CHC users 2% were on ultra-low dose pills, 90% low dose pills, 7% high dose pills, and 12.7% patches. There were no CHC ring users. There were no VTE events in the CHC or CHC+AF groups. There was one VTE event in the AF group. This patient had a remote VTE due to lupus and Factor V Leiden. She was anticoagulated and had IVC filter in place. HMB resulted from anticoagulation that was unresponsive to progesterone therapy alone. Hematology then allowed for use of AF, which subsequently controlled her HMB without recurrent VTE. <h3>Conclusions</h3> The incidence of VTE was low among adolescents with HMB (0.04%). We found no cases of VTE among users of CHC+AF. Screening for thrombophilia risk factors is important, and our study suggests CHC+AF does not result in increased risk of VTE among adolescents with HMB.

Migraine start, course and features over the cycle of combined hormonal contraceptive users with menstrual migraine \u2013 temporal relation to bleeding and hormone withdrawal: a prospective diary-based study

BackgroundMany studies have described the features of menstrually-related migraines (MRM) in the natural cycle and the efficacy of prevention. MRM in combined hormonal contraceptive (CHC) users has scarcely been researched. Estrogen and progestin withdrawal in CHC users are both more abrupt and from higher hormone levels compared with the natural cycle. An advantage for prevention of MRM in CHC users is that the hormone withdrawal is predictable. It is unknown, whether the attacks during the hormone-free interval are associated with the hormone withdrawal or onset of bleeding. Improved understanding of this relation might contribute to better define and shorten the time interval for prevention.MethodsFor this prospective diary-based trial we collected migraine and bleeding data from CHC users with MRM in at least two of three cycles. We analyzed frequency of migraines over the whole CHC cycle. During the hormone-free phase the relation between onset of migraine and onset of bleeding was studied. We compared pain intensity and identified prolonged-migraine attacks during hormone use and the hormone-free phase.ResultsDuring the hormone-free interval the number of migraine days and the pain score/migraine day were significantly higher in comparison with the mean during hormone use. The prevalence of migraine attacks was fourfold on hormone-free days 3–6. Migraine typically started on days 1–4. Migraine in relation to bleeding mostly occurred on days − 1 to + 4. In 78% of the cycles the first migraine day occurred during bleeding days 1 ± 2 and 48% started on days − 1 and day 1. The predictability of the first bleeding day was very high.ConclusionThe day of hormone-withdrawal migraine and the first bleeding day are highly predictable in CHC users. Migraine onset is mostly day − 1 and 1 of the bleeding and on days 1–4 of the hormone-free interval. Migraine attacks of CHC users in the hormone-free interval are severe and long lasting. Further trials are necessary to investigate if this knowledge can be used to optimise prevention.

Impact of Combined Hormonal Contraceptive Use on Weight Loss: A Secondary Analysis of a Behavioral Weight-Loss Trial.

This study aimed to perform a preliminary investigation of the impact of combined hormonal contraceptive (CHC) use on weight loss during an 18-month behavioral weight-loss trial. Adults (n = 170; 18-55 years; BMI 27-42 kg/m2 ) received a weight-loss intervention that included a reduced-calorie diet, a progressive exercise prescription, and group-based behavioral support. Premenopausal women (n = 110) were classified as CHC users (CHC, n = 17) or non-CHC users (non-CHC, n = 93). Changes in weight were examined within groups using a linear mixed model, adjusted for age and randomized group assignment. At 6 M, weight was reduced from baseline in both CHC (mean, -6.7 kg; 95% CI: -9.8 to -3.7 kg) and non-CHC (-9.1 kg; -9.1 to -6.4 kg). Between 6 and 18 M, CHC regained weight (4.9 kg; 0.9 to 8.9kg), while weight remained relatively unchanged in non-CHC (-0.1 kg; -1.8 to 1.6 kg). At 18 M, weight was relatively unchanged from baseline in CHC (-1.8 kg; -7.3 to 3.6 kg) and was reduced from baseline in non-CHC (-7.9 kg; -10.2 to -5.5 kg). In this secondary data analysis, CHC use was associated with weight regain after initial weight loss. Prospective studies are needed to further understand the extent to which CHC use influences weight loss and maintenance.