Abstract
Objectives:
Although many people with OUD may believe they are infertile due to chronic opioid use contributing to menstrual irregularities, minimal data exists on how opioid cessation and OUD treatment may impact fertility. We examine fertility perceptions and menstrual cycle characteristics of treatment-seeking women with OUD.
Methods:
Data came from the Survey of Key Informants’ Patients (SKIP) Program, a US-based opioid surveillance study of individuals newly entering OUD treatment. The SKIP Program recruits adults newly entering treatment for OUD to complete anonymous, self-report surveys. Respondents who identified as female or non-binary from 49 SUD treatment programs in 25 states were asked questions about their perceptions of fertility and menstrual cycle characteristics from January to March 2024. Analyses were restricted to women 18–49 years old with no history of hysterectomy.
Results:
Of 637 respondents, 179 met criteria for analysis. The average age was 34.8 years (SD 7.0), 15.1% identified as Black, 10.6% Native American/Alaskan Native, and 58.7% White. The most common OUD treatment was buprenorphine (47.5%). Of respondents, 51.5% (85/165) did not believe they could become pregnant. Half (57.0%, 102/179) reported either irregular or no menstrual cycles in the year prior. Respondents who believed they could become pregnant were younger (32.0 vs. 37.1 y, P < 0.0001) than those who believed they were infertile.
Conclusions:
Menstrual irregularities and perceptions of infertility were high among a nationally representative sample of treatment-seeking women with OUD, highlighting the need for patient-provider discussions about these topics in the context of OUD treatment.
Keywords: fertility, menstrual cycles, opioid use disorder, pregnancy
Women with opioid use disorder (OUD) have higher rates of unintended pregnancies and lower rates of contraception use than the general population.1,2 At the same time, chronic opioid use is associated with menstrual cycle irregularities (amenorrhea and reduced probability of conceiving), likely through suppression of the hypothalamic-pituitary-ovarian axis.3–5 Treatment-seeking women with OUD often believe they cannot become pregnant,3,6 a perception that may stem from engagement in unprotected sex without conceiving while using opioids.7,8 For women entering OUD treatment, whether or not medications are used, accurate understanding of fertility status is critical for reproductive planning.
A significant gap exists in our understanding of women’s knowledge of their fertility and menstrual cycles while using opioids and after initiating treatment. Although studies call for increased access to and uptake of contraception by women with OUD to prevent pregnancy,2,7,8 few prioritize women’s lived experiences, and existing OUD-related fertility research has disproportionately focused on men.9 Understanding women’s fertility perceptions and menstrual experiences is not only a reproductive justice issue, but also essential for supporting reproductive autonomy, whether women wish to conceive, delay pregnancy, or avoid pregnancy altogether. We aim to describe women’s self-reported fertility perceptions and menstrual cycle characteristics among individuals seeking treatment for OUD.
METHODS
Study Sample
Data were sourced from the Survey of Key Informants’ Patients (SKIP) Program, a national opioid surveillance study of individuals entering treatment with a primary diagnosis of OUD that began in 2011 and includes 154 treatment programs yielding ~3000 respondents annually from 47 states. This serial, cross-sectional survey is part of the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) system, owned by Denver Health and Hospital Authority, and includes programs that collect and analyze US drug trend data.10 The SKIP Program recruits individuals aged at least 18 years who are newly entering treatment with a primary diagnosis of OUD to complete anonymous, self-report surveys (85% response rate). Data have been validated against other national drug surveillance programs.10,11 Respondents from 49 SUD treatment programs in 25 states were administered questions on fertility perceptions and menstrual cycle characteristics added to surveys distributed from January to March 2024.
Measures
Survey items, informed by the authors’ clinical experience, assessed: perceived ability to become pregnant (yes/no) and reasons for this belief; menstrual cycle presence in the prior 12 months; cycle regularity (21–28 d vs. < 21 or > 35 d); and reasons for amenorrhea (eTable 1, Supplemental Digital Content 1, http://links.lww.com/JAM/A816). Demographic factors included age, race/ethnicity, pregnancy history, OUD treatment type, and treatment for psychiatric disorders. Although current contraceptive use was not explicitly assessed, respondents could self-report use of long-acting reversible contraception (LARC; intrauterine devices or implants) and permanent sterilization.
Study Sample and Analysis
Of 637 total respondents, 222 identified as women or non-binary, of which 184 were 18–49 years old, and 179 had an intact uterus (no history of hysterectomy; eFigure 1, Supplemental Digital Content 2, http://links.lww.com/JAM/A817). Respondents who reported use of LARC or permanent sterilization (tubal ligation, bilateral salpingectomy, or Essure) were included in the analytic sample due to the reversible nature of LARC and the possibility of assisted reproductive technologies among people with permanent sterilization allowing potential future pregnancies. We used summary statistics, proportions, and means to summarize survey responses. To identify covariates (demographics, comorbidities, pregnancy history, and menstrual cycle characteristics) associated with perceived fertility, we used t tests for continuous variables and chi-square and Fisher exact tests for categorical variables. SAS Proc 9.4 was used for all analyses. All study materials and protocols were approved by Washington University in St. Louis’ institutional review board.
RESULTS
Among 179 respondents of childbearing age with an intact uterus, 32 reported permanent contraception, 3 reported LARC use, and 2 reported other contraceptive methods. Mean age was 34.8 years (SD 7.0); 15.1% identified as Black, 10.6% as Native American/Alaskan Native, and 58.7% as White. OUD treatments included buprenorphine (47.5%), psychosocial treatment without medication (24.0%), methadone (24.0%), and extended-release naltrexone (5.0%; Table 1).
TABLE 1.
Demographics, Fertility Perceptions, and Menstrual Cycle Characteristics of Women With Opioid Use Disorder (N = 179)*
| Variable | N (%) |
|---|---|
| Age (mean, SD) | 34.8 (7.0) |
| Race | |
| Asian | 2 (1.1) |
| Black | 27 (15.1) |
| Latinx | 11 (6.2) |
| Multiracial | 12 (6.7) |
| Native American/American Indian | 19 (10.6) |
| Other | 3 (1.7) |
| White | 105 (58.7) |
| Treatment type for OUD | |
| Buprenorphine | 85 (47.5) |
| Methadone | 43 (24.0) |
| Naltrexone (long-acting depo) | 9 (5.0) |
| Psychosocial without medication | 43 (24.0) |
| Ever treated for a psychiatric disorder (n = 171) | 106 (62.0) |
| No. pregnancies (n = 170) | |
| 0 | 30 (17.7) |
| 1 | 23 (13.5) |
| 2–3 | 68 (40.0) |
| 4–5 | 28 (16.5) |
| 6 or more | 21 (12.4) |
| Fertility perceptions (n = 165) | |
| Does not believe can become pregnant | 85 (51.5) |
| Reason for belief of infertility (n = 85) | |
| Does not have periods | 10 (11.8) |
| Has not gotten pregnant having regular unprotected sex | 11 (12.9) |
| Was told by a doctor | 10 (11.8) |
| Partner cannot have children | 3 (3.5) |
| Not sexually active with a male partner | 8 (9.4) |
| Permanent sterilization procedure | 32 (37.6) |
| LARC method | 3 (3.5) |
| Birth control method | 2 (2.3) |
| Menstrual cycle characteristics (n = 179) | |
| Had a menstrual period in the last 12 mo | 133 (74.3) |
| Regular periods | 77 (57.9) |
| Irregular periods† | 56 (42.1) |
| No menstrual period in the last 12 mo | 46 (25.7) |
| Reasons for amenorrhea or irregular menstrual cycles in the past 12 mo (n = 93) | |
| Opioid use | 22 (23.7) |
| Unsure | 21 (22.6) |
| Pregnancy or breastfeeding | 5 (5.4) |
| Medical reasons | 8 (8.6) |
| Other reasons‡ | 11 (11.8) |
Denominator is 179 respondents unless otherwise indicated.
More than 35 days, < 21 days, or so irregular cannot calculate interval.
Other reasons include being on drugs (not specifically opioids), birth control, overweight.
OUD indicates opioid use disorder.
Most respondents reported at least one prior pregnancy (82.4%); however, 51.5% (85/165) did not believe they could become pregnant, most commonly due to permanent contraception (37.6%). Among respondents not using LARC or permanent contraception (n = 130), 38.5% perceived infertility, most often citing lack of conception despite regular unprotected sex (22.0%). Overall, 74.3% reported at least one menstrual cycle in the prior 12 months; 42.1% reported irregular cycles and 25.7% amenorrhea. Opioid use was the most commonly cited reason for amenorrhea or irregular cycles (22/93; 23.7%).
Respondents perceiving infertility were older than those perceiving fertility (37.1 vs. 32.0 y; P < 0.0001). Perceived fertility was more common among respondents with zero or one prior pregnancy compared to respondents with 2 or more pregnancies (19.7% vs. 14.6% and 22.4% vs. 7.2%, respectively; P = 0.03).. Perceived fertility did not differ by race/ethnicity, menstrual regularity, OUD treatment type, or psychiatric history (Table 2).
TABLE 2.
Demographics and Menstrual Cycle Characteristics of Women With Opioid Use Disorder by Belief Can Become Pregnant (n = 165)
| Believe You Can Become Pregnant | |||
|---|---|---|---|
| Yes | No | ||
| N (%) | N (%) | P | |
| Age (mean, SD) | 32.0 (7.1) | 37.1 (6.2) | < 0.0001 |
| Race | |||
| Asian | 1 (1.3) | 1 (1.2) | |
| Black | 14 (17.5) | 13 (15.3) | |
| Latinx | 5 (6.3) | 5 (5.9) | |
| Multiracial | 5 (6.3) | 7 (8.2) | |
| Native American/American Indian | 8 (10.0) | 10 (11.8) | |
| Other | 0 | 2 (2.4) | |
| White | 47 (58.8) | 47 (55.3) | 0.9328 |
| Treatment type for OUD | |||
| Buprenorphine | 37 (46.3) | 42 (49.4) | 0.6845 |
| Methadone | 18 (22.5) | 21 (24.7) | 0.7389 |
| Naltrexone (long-acting depo) | 5 (6.3) | 4 (4.7) | 0.7407 |
| Psychosocial without medication | 21 (26.3) | 19 (22.4) | 0.5594 |
| Ever treated for a psychiatric disorder (n = 159) | 48 (61.5) | 51 (63.0) | 0.8530 |
| No. pregnancies (n = 159) | |||
| 0 | 15 (19.7) | 12 (14.5) | 0.0314 |
| 1 | 17 (22.4) | 6 (7.2) | |
| 2–3 | 25 (32.9) | 38 (45.8) | |
| 4–5 | 13 (17.1) | 14 (16.9) | |
| 6 or more | 6 (7.9) | 13 (15.7) | |
| Had a menstrual period in the last 12 mo | 64 (80.0) | 62 (72.9) | 0.2861 |
| Regular periods | 36 (56.3) | 39 (62.9) | 0.4469 |
| Irregular periods* | 28 (43.8) | 23 (37.1) | |
| No menstrual period in the last 12 mo | 12 (15.0) | 21 (24.7) | 0.1193 |
| Reason has not had a period in the past 12 mo (n = 85) | |||
| Opioid use | 14 (34.2) | 6 (13.6) | 0.0259 |
| Unsure | 8 (19.5) | 12 (27.3) | 0.3993 |
| Pregnancy or breastfeeding | 3 (7.3) | 0 | 0.1079 |
| Medical reasons | 1 (2.4) | 5 (11.4) | 0.2036 |
| Other reasons† | 5 (12.2) | 6 (13.6) | 0.8432 |
More than 35 days, < 21 days, or so irregular cannot calculate interval.
Other reasons include being on drugs (not specifically opioids), birth control, overweight
OUD indicates opioid use disorder.
DISCUSSION
Reproductive-age women with OUD in this study shared important insights about their menstrual history and perceptions of fertility after treatment entry. Over a third of respondents without permanent sterilization believed they were infertile, almost 3 times higher than estimates from women in the general population.12 The most common reason for this belief among respondents not using LARC or permanent contraception was prior experiences of not conceiving despite regular unprotected sex, which could reflect reduced ability to conceive related to OUD or other unmeasured factors. Consistent with this belief, two-thirds reported irregular or absent periods in the prior year, with nearly 30% attributing menstrual irregularities to opioid use. Unexpected pregnancy under these circumstances can destabilize early recovery, underscoring the need to address fertility perceptions and reproductive health needs. Finally, increasing age and number of prior pregnancies were associated with perceived infertility, consistent with the known association between these factors and permanent sterilization.13
Potential contributors to amenorrhea among people who use opioids include severe stress and untreated metabolic disturbances related to barriers to care.14 Studies suggest opioids have differential effects on the hypothalamic-pituitary-ovarian (HPO) axis. Methadone has been associated with increased amenorrhea and menstrual irregularity, although its effects on fecundability may differ from illicit heroin use due to more consistent dosing.4 Limited data suggest possible HPO axis adaptation, with longer methadone exposure associated with return of menstrual cyclicity.4,5 However, most existing data reflect older opioid formulations. Substantial gaps remain regarding individuals using potent synthetic opioids such as fentanyl, poly-substance use, and treatment with buprenorphine or naltrexone, limiting clinicians’ ability to counsel patients on menstrual and fertility expectations during treatment.
Study strengths include amplifying women’s experiences on a largely unexplored issue affecting women’s health and families in a racially, ethnically, and geographically diverse sample of treatment-seeking women with OUD. Study limitations include the self-reported nature of survey data and limited data on other factors that may impact fertility and menstruation including pregnancy intentions and contraception use. Despite these limitations, women’s fertility perceptions represent their authentic beliefs that cannot be easily captured with other measures.
CONCLUSIONS
This analysis is an important first step in documenting fertility perceptions and menstrual experiences among treatment-seeking women with OUD. These findings have important implications for sexual and reproductive health behaviors at a time when women are unlikely to have their reproductive health needs addressed.15 Understanding women’s fertility experiences during OUD treatment can guide research and inform clinician counseling on opioid-related fertility effects, supporting women in their reproductive goals.
Supplementary Material
Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal’s website, www.journaladdictionmedicine.com.
Acknowledgments
This work was sponsored by the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System. The RADARS System is the property of Denver Health and Hospital Authority, a political subdivision of the State of Colorado. Effort for some personnel was supported by grants K23 DA053433 (PI: J.B.K.), 1K12DA061526-01 (X.A.L.), and K08 DA061258 (PI: K.X.) but these grants did not fund the analyses.
Footnotes
The authors report no conflicts of interest.
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