A pioneer of hormonal contraception: Joseph W. Goldzieher.

On 19 July, 2024, at the age of almost 105 years, Joseph W. Goldzieher, the last survivor of the group of pioneers who created oral contraception, peacefully passed away. Here we briefly reconstruct the salient points in his long, productive life, and highlight his achievements in the development of hormonal contraception. His work is indissolubly enshrined in the complex history of hormonal contraception, from the first, fundamental observations, to the first clinical trials, both in the form of combined oestrogen-progestin oral pills and long-acting injectable contraceptives. After Pincus and his Group created an oral contraceptive containing an oestrogen and a progestin, Goldzieher was the second international scientist to conduct clinical trials of the new modality. He teamed-up with investigators in Mexico creating a fruitful, long-lasting collaboration. They produced evidence that ovulation inhibition could be achieved with all the progestins used at the time. Of importance, he was among the first to explore the possibility of using oestrogens to block ovulation, and developed the concept of sequential contraception. For all this lifetime of work, we believe he deserves to be named a 'giant in reproductive endocrinology'.

Assessing Student and Patient Perspectives on Pharmacist Prescribed Hormonal Contraceptives.

BACKGROUND: Increasing convenient, accessible, and cost effective contraceptive access is critically important. Two-thirds of US states permit pharmacists to prescribe hormonal contraceptives. Community pharmacies are ideal settings for patients to be offered contraceptive therapeutic options including hormonal contraceptives, emergency contraception (EC), and over-the-counter (OTC) oral contraception. OBJECTIVE: The objective of this study was to assess college student and community pharmacy patients' perspectives on pharmacist prescribed hormonal contraceptives, likelihood of accessing contraceptives from a pharmacist, and perspectives regarding EC and OTC oral contraception. METHODS: The researchers conducted an observational study distributed to college students and patients accessing care at community-based pharmacies from October 2022 to February 2023. The survey population included those who were 18 years or older, English speaking, and recruited both in person and online. Survey questions assessed barriers to contraception access, perspectives towards pharmacist prescribed hormonal contraception, likelihood of receiving pharmacist prescribed hormonal contraception as well as EC and OTC oral contraception at the community pharmacy. Results from the pharmacist and clinician surveys were previously published, therefore this report will focus on the student and patient data. RESULTS: Ninety-one percent of all respondents strongly agreed or agreed with pharmacist-prescribed hormonal contraception. Students and patients reported convenience, time saving, and money saving as reasons for obtaining from their pharmacist. In regard to EC, 36% reported having ever purchased from a pharmacy and 58% were extremely or somewhat likely to purchase OTC oral contraception. CONCLUSIONS: The majority of students and community pharmacy patients surveyed in Rhode Island support pharmacist prescribed hormonal contraceptives. State-level policy advancements with reimbursement for services provide pharmacists an opportunity to provide contraceptive care for all people.

Influences on ethnic minority women's experiences and access to contraception in the UK: a systematic qualitative evidence synthesis.

BACKGROUND: Accessible contraception is critical for promoting the health and well-being of women and their families. In the UK, contraception is free at the point of access, but only 55% of pregnancies are planned, with negative implications for maternal and infant outcomes. In general, women from ethnic minorities use contraceptives less than white women. Barriers to the uptake of contraceptives have been identified, including perceived poor information from healthcare professionals and concerns about side effects. However, most studies do not include representative proportions of women from ethnic minorities. Evidence suggests that ethnic minority (EM) women feel targeted and coerced by healthcare professionals regarding contraception. METHODS: A systematic search of Medline, Embase, and PsycINFO via Ovid, CINAHL, and Web of Science was conducted to identify primary qualitative and mixed-methods studies exploring ethnic minority women's experience of contraception in the UK. The data were charted using thematic analysis, using both summary and synthesis. RESULTS AND CONCLUSIONS: 16 studies met the inclusion criteria, including the perspectives of 717 participants from an ethnic minority. Four overarching themes were developed: contraceptive knowledge, beliefs, family, and services. Similar to women in general, ethnic minority women have concerns about side effects, especially infertility, value the perspectives of their peers and male partners, and express a preference for female healthcare professionals. Novel perspectives included conflicting ideas about the influence of religion and stereotyping of ethnic minority women. Culturally competent consultations and a better understanding of hormonal hesitancy are essential.

Reproductive Management of Reptiles.

Research in reproductive management of reptiles has focused on developing and investigating feasible methods that can be used in clinical practice and laboratory settings, including sexing in monomorphic species and methods of artificial insemination in endangered reptile species. In captive pet reptile species, research is focused on hormonal regulation of reproductive activity. Gonadotropin-releasing hormone (GnRH) agonist implants may temporarily suppress reproductive endocrine system (eg, circulating concentrations of estrogens and progesterone) in female green iguanas but did not influence male iguana behavior and plasma testosterone levels. Additionally, it did not suppress reproductive activity of females of other lizard species (eg, leopard geckos).

Pharmacist-Prescribed Hormonal Contraception: A Survey of Perceptions of Georgia Community Pharmacists and Non-Community Pharmacists.

Pharmacist-prescribed hormonal contraception (HC) is supported by a majority of pharmacists and pharmacy students; however, few studies have evaluated perceptions of non-community pharmacists, or differences in geographic areas. The primary objective of this study is to assess differences between community and non-community pharmacists in perceptions of pharmacist-prescribing HC in Georgia, a state that does not currently permit this practice. Secondary objectives include assessment of community pharmacist interest in prescribing HC, and differences in perceptions between pharmacists in metropolitan and nonmetropolitan areas. A survey was emailed in early 2022 to 2592 Georgia pharmacists, with Likert questions assessing interest, perceptions, comfort, and perceived barriers regarding pharmacist-prescribed HC. Chi square testing identified differences between groups. The completed survey response rate was 11.8%. Regardless of practice site, a majority agreed that pharmacists are well trained to prescribe HC (community 61.8% vs. non-community 68.1%, p = 0.25) and provision of HC services is within pharmacists' scope (community 73.6% vs. non-community 74.2%, p = 0.90). Overall, metropolitan and nonmetropolitan community pharmacist perceptions were similar; however, more metropolitan pharmacists believed pharmacists are well trained to prescribe HC (66.7% vs. 48.7%, p = 0.049) and that it is within their scope of practice (78.1% vs. 61.5%, p = 0.045). In summary, the majority of pharmacists, regardless of practice type, believe that pharmacists are prepared to prescribe HC and that it is a part of pharmacists' professional scope of practice.

The Most Common Side Effects, Concerns and Discontinuation Patterns of Oral Contraceptive Pills Among Polish Women: A Cross-Sectional Study.

Objective: Over the decade, variety and effectiveness of contraception methods have greatly improved, resulting in increased popularity of oral contraceptive pills (OCPs). However, hormonal contraception carries the risk of multiple side effects. The lack of sufficient knowledge often leads to the development of health concerns, which can affect patient's adherence. The aim of our research was to describe a side effect profile of OCPs and assess the most frequent concerns and discontinuation reasons in Polish women. The survey included questions regarding OCPs utilization patterns, side effects, health concerns and attitudes of the responders. Materials and methods: This cross-sectional study was based on a survey, which was distributed online and open from 29 April to 15 May 2022. The survey included questions regarding OCPs utilization patterns, side effects, health concerns and attitudes of the responders. Results: Out of 1699 respondents, the current OCPs intake was reported by two thirds of women and 22% had a history of using them in the past. Seventy-nine percent of all OCPs users experienced adverse effects while 9% reported having concerns about safety and potential adverse effects. Decreased libido and weight gain were the most significant reasons for ceasing hormonal contraception. Moreover, the most common concerns and the most unfavorable side effects varied in different age groups. The occurrence of anxiety depended on age and education. Conclusion: Healthcare professionals prescribing OCPs should provide their patients with comprehensive counseling. Understanding and addressing concerns of young women can improve their compliance and reduce the number of unintended pregnancies.

Effects of hormonal contraception on mood and sexuality.

The impact of hormonal contraception on mental and sexual health has long been either ignored or considered to be much less important than the cardiovascular, metabolic and cancer risks. In recent years the interest in these side effects, having an impact on the quality of life of users, has grown due to several reasons. In the last decades different scientific approaches to gain empirical evidence about the type and extent of negative effects of hormonal contraceptives on mood and sex did not result in clear evidence-based statements due to the complexity of the interaction between contraceptive methods and mental and sexual health (inconsistent measurement of patient reported outcomes, multiplicity of intervening variables etc). Based on an understanding of the biological, psychological and sociocultural factors contributing to the mental and sexual health of the individual user, and the individual impact of hormonal contraception, which can have negative, positive or neutral effects on mood and sexuality, an individualized approach is proposed to integrate mental and sexual health into the practice of contraceptive counselling and care.

Use of systemic hormonal contraception and risk of attempted suicide: a nested case-control study.

Evidence regarding the role of hormonal contraception (HC) as a risk factor for attempted suicide is inconclusive. Thus, this study aimed to assess the associations of use of different types of systemic HC with the risk of attempted suicide in women aged 15-49 years. Data on a population-based cohort (n = 587,823) of HC users and non-users in 2017 was derived from national registers in Finland. In a nested case-control design we examined the risk of attempted suicide in relation to current HC use (past six months) via multivariable conditional logistic regression models. During the follow-up (from 2018 to 2019) there were 1.174,346 million person-years of which 818 cases of suicide attempts were observed (incidence rate: 0.70 per 1000 person-years). Use of HC, especially combined hormonal contraceptives, was not associated with a higher risk of attempted suicide compared to non-use (OR 0.68, 95% CI 0.45-1.02) after controlling for marital status, socioeconomic status, education, chronic diseases, recent delivery, recent psychiatric hospitalizations, and current use of psychotropic medications. In women without psychiatric history, current HC use (OR 0.73, 95% CI 0.58-0.91), especially ethinylestradiol-containing preparations (OR 0.54, 95% CI 0.40-0.73), was associated with a lower risk of attempted suicide. After adjusting for recent psychiatric hospitalizations and use of psychotropic medications, current use of progestin-only preparations was not associated with attempted suicide. In conclusion, current HC use was not associated with an increased risk of attempted suicide in fertile-aged women.

A revisit of knowledge, attitude and practice of emergency contraception in Hong Kong.

OBJECTIVES: To revisit women's knowledge, attitudes and practices (KAP) regarding emergency contraception (EC) in Hong Kong. The research sought to provide insights for improving the accessibility and quality of EC services. STUDY DESIGN: A cross-sectional study, where self-administered questionnaires were distributed at a major community sexual and reproductive health service in Hong Kong over a 3-month period between July 2023 and October 2023. Descriptive and regression analyses were used. RESULTS: Of 1127 respondents, the majority (n=1057, 93.8%) reported using contraception and 513 (45.6%) had used EC. The main contraceptive methods used were male condoms and oral contraceptive pills. The majority (n=1035, 91.8%) of respondents demonstrated awareness about EC and 938 (83.2%) participants correctly reported the timeframe for oral EC. Around two-thirds reported the internet as being their leading source of EC knowledge. Over 93% of respondents advocated for enhancing public awareness. Acceptance of non-traditional means of obtaining EC, such as over-the-counter provision (51.3%), pharmacy provision (49.8%) and telemedicine consultation (43.1%), were higher than face-to-face EC consultations (32.9%). CONCLUSIONS: Family planning service users' characteristics and KAP regarding EC have significantly changed over the last 20 years. Women now demonstrate greater awareness, knowledge and openness regarding EC, indicating improved readiness for more liberal delivery of EC nowadays. This study highlights the need for restructuring EC service provision in Hong Kong to address women's changing preferences and contraceptive needs, and to minimise barriers to EC access. We recommend reclassifying emergency contraceptive pills as non-prescription drugs in Hong Kong to align with international practice.

An age-related nomogram for antral follicle count: an observational study of 3821 women.

RESEARCH QUESTION: What is the relationship between antral follicle count (AFC) and chronological age, and what are the expected values for AFC? DESIGN: This was a retrospective cohort study at a specialist gynaecological ultrasound centre in London, UK. Women presenting to a gynaecology diagnostic unit for investigation of symptoms or routine check-up, and undergoing transvaginal ultrasound (TVUS) examinations, between 1 January 2017 and 22 September 2022 were included in this study. RESULTS: In total, 8821 TVUS records from 7573 patients were analysed. The relationship between AFC and age was estimated to develop an AFC nomogram independent of the stage in the menstrual cycle. AFC corresponding to the 10th, 25th, 50th, 75th and 90th centiles for each patient and age group were calculated. Both nomogram and condition-specific populations displayed a Gaussian relationship between AFC and age. For the nomogram population (scans n = 4256, patients n = 3821), a peak median AFC of 30 was observed between 21-23 years of age. The AFC distribution of the group with previous ovarian cystectomy (scans n = 534, patients n = 443) was found to be significantly different compared with the nomogram population (P < 0.0001). However, the same did not hold true for those on hormonal contraception (scans n = 566, patients n = 534) (P = 0.43). CONCLUSIONS: An AFC nomogram reporting median and interquartile values for AFC by chronological age across the reproductive years was developed. This is a useful tool for providing counselling for those undergoing ovarian reserve assessments, and can be taken any time in the menstrual cycle, including in women on hormonal contraceptives or who have undergone previous ovarian cystectomy.

Comparing English- and Spanish-Reading Patients' Comprehension of the Drug Facts Label for a New Over-The-Counter Oral Contraceptive.

BACKGROUND: Health literacy is known to impact health outcomes in a multitude of ways and is impacted by language barriers. Lower health literacy is also associated with higher rates of unintended pregnancies. A progestin-only oral hormonal contraception product, norgestrel (Opill-Perrigo), was approved for over-the-counter (OTC) use in the United States in July 2023. OBJECTIVE: (s): The objective was to utilize a knowledge assessment survey to determine participants' comprehension of norgestrel from its drug facts label and compare the comprehension between primarily English- and Spanish-reading participants. METHODS: A 7-item knowledge assessment was developed and distributed to English and Spanish readers at one site within a network of federally qualified health centers. English-reading participants completed the English survey alongside use of an English copy of norgestrel's drug facts label. Spanish-reading participants completed the Spanish survey and were randomized in a 1:1 fashion to either receive an English or Spanish copy of norgestrel's drug facts label. RESULTS: The English-reading/English label (E/E) group had a higher level of comprehension of norgestrel's drug facts label compared to the Spanish-reading/English label (S/E) or Spanish-reading/Spanish label (S/S) groups. CONCLUSION: Differences exist in OTC label comprehension for norgestrel based on primary language able to be read. Advocacy for OTC labels to be readily available in languages other than English is imperative to mitigate unintended pregnancies associated with lower levels of health literacy.

The impact of using the levonorgestrel-releasing intrauterine device on the incidence of acne in adolescents and young women.

PURPOSE: To evaluate the impact of levonorgestrel-releasing intrauterine device (LNG-IUD) use on the incidence of acne in adolescents and young women. METHODS: A narrative review was conducted in PubMed, Embase, Cochrane, and SciELO assessing the incidence of acne in adolescents and young women using LNG-IUD (13.5, or 19.5 mg, or 52 mg). Cohort, cross-sectional studies, clinical trials, and meta-analyses were included, without a date limit. Studies that didn't evaluate women in the age of interest were excluded. Only articles in English were selected. RESULTS: Nine articles were included in this narrative review. Only clinical trials, cohort studies, and cross-sectional studies were evaluated. Two cross-sectional studies evaluated the incidence of acne in women using any contraceptive methods, with the incidence of acne being 36% in women aged 17 to 47 using LNG-IUD in one study. In another study, acne incidence ranged from 2 to 8% in women using any contraceptive methods, with higher rates in younger women and LNG-IUD users. The incidence of acne varies and participants between 16 to 35 years were more likely to report new acne or worsening of pre-existing acne. In a prospective cohort study of women between 16 and 24 years, acne was a common adverse effect, with 44% in the first year. CONCLUSION: The data indicate variability in the incidence of acne among LNG-IUD users, with a higher prevalence observed in younger women. Further research should focus on the effects of LNG-IUD on acne in young populations, with rigorous study designs and consideration of previous contraceptive use.

The levonorgestrel-releasing intrauterine device (LNG-IUD) is an important tool in the prevention of unplanned pregnancies in adolescents and young women. Acne is a possible adverse effect that could lead to discontinuation of the method.

Dysmenorrhea, a Narrative Review of Therapeutic Options.

Dysmenorrhea is the most common pathology women of childbearing age face. It is defined as painful uterine cramping associated with menstruation. Primary dysmenorrhea occurs in the absence of an organic cause, whereas secondary dysmenorrhea is pelvic pain associated with an underlying pelvic pathology. The purpose of this review is to discuss the pathophysiology of dysmenorrhea and provide a discussion of pharmacologic and non-pharmacologic treatment options. Prostaglandins play a large role in the pathophysiology of dysmenorrhea by causing myometrial contraction and vasoconstriction. The first-line treatment for dysmenorrhea is with nonsteroidal anti-inflammatory drugs due to the inhibition of cyclooxygenase enzymes, thereby blocking prostaglandin formation, as well as hormonal contraception. Other pharmacologic treatment options include Paracetamol, as well as Gonadotrophic Release Hormone Analogs, which are typically used in the treatment for endometriosis. Non-pharmacologic treatments with strong evidence include heat therapy and physical exercise. There are less evidence-based data behind other modalities for treating dysmenorrhea, such as dietary supplements, acupuncture, and transcutaneous nerve stimulation, and these methods should be used in conjunction with first-line therapy after a discussion of risks and benefits. Lastly, for women who fail medical management, surgical options include endometrial ablation, presacral neurectomy, and laparoscopic uterosacral nerve ablation. Further research is needed to measure the socioeconomic burden of dysmenorrhea on the healthcare system and to evaluate the efficacy of treatment combinations, as a multi-modal approach likely provides the most benefit for women who suffer from this condition.

Digital training for self-injectable contraceptives: a feasibility and acceptability pilot study.

BACKGROUND: Self-injectable contraceptives, namely subcutaneous depot medroxyprogesterone acetate 104 mg micronised formulation delivered via uniject system, reduce the need to travel to a facility for contraceptive access, but the initial, in-person, training may be a barrier to starting this method. This article reports on a small, exploratory pilot in Kenya to test the feasibility and acceptability of digital self-injection training. METHODS: Participants (n=11) who were currently using injectable contraceptives, intramuscular depot medroxyprogesterone acetate 150 mg injected by a healthcare worker, received digital self-injection training from a trained clinician via a WhatsApp video call. Participants administered a simulated self-injection on a model and an actual self-injection (under supervision) on themselves. The participants' self-injection proficiency, a measure of the feasibility of remote training, was documented using a checklist, and participants were administered a questionnaire about their training experience. The training was observed, and content analysis was used to understand the functionality of training. RESULTS: All participants were proficient when performing the self-injection on themselves after receiving the remote training and reported that the training was acceptable. A barrier to training via a video call was lack of access to quality digital devices. Eight training 'lessons learnt' emerged from the training observations. CONCLUSIONS: Training participants to administer self-injectable contraceptives via WhatsApp video call was feasible and acceptable. Training lessons learnt offer pragmatic adaptations for communicating about a practical skill via a digital channel. Further research is needed to ascertain the efficacy of digital training for self-injection and feasibility and acceptability for wider groups.

A Review of Concordance and Quality in Clinical Guidelines for Hormonal Contraceptives to Mitigate Drug-Drug Interactions in Women With Epilepsy.

PURPOSE: Concomitant use of hormonal contraceptive agents (HCAs) and enzyme-inducting antiepileptic drugs (EIAEDs) may lead to contraceptive failure and unintended pregnancy. This review identified and evaluated concordance and quality of clinical treatment guidelines related to the use of HCAs in women with epilepsy (WWE) receiving EIAEDs. METHODS: Relevant clinical guidelines were identified across four databases and were independently evaluated for quality utilizing the AGREE-II protocol instrument. Quality in this context is defined as the rigor and transparency of the methodologies used to develop the guideline. Guidelines were further assessed in terms of concordance and discordance with the latest body of knowledge concerning the use of hormonal contraception in the presence of EIAEDs. RESULTS: A total of n = 5 guidelines were retrieved and evaluated. Overall guideline scores ranged from 17% to 92%, while individual domain scores ranged from 0% to 100%. Contraceptive guidelines consistently recommended the use of intrauterine systems and long-acting injectables in the presence of EIAEDs, recommended against the use of oral, transdermal, and vaginal ring contraceptives, and differed regarding recommendations related to implants. Guidelines agreed regarding recommendations that women treated with EIAEDs should receive intrauterine systems and long-acting injectables; however, the suggested frequency of administration of injectable contraceptives differed. The use of intrauterine systems in this population is supported by evidence, but there is uncertainty surrounding the use of long-acting injectables and contraceptive implants. CONCLUSIONS: To mitigate the risk of unintended pregnancy and its consequences, recommendations related to implants and long-acting injectable contraceptives should be evidence-based.

The association between lifestyle factors and the composition of the vaginal microbiota: a review.

PURPOSE: The vaginal microbiota offers valuable insights into women's sexual health and the risk of developing sexually transmitted infections (STIs) and bacterial vaginosis. Despite the public health implications of changes in the vaginal environment, existing data on this topic remain sparse. METHODS: Following the PRISMA statement guidelines, we consulted five bibliographic databases, focusing on five main daily habits and behaviors. We included only studies published up to October 2023, investigating the influence of personal hygiene, sexual behaviors, hormonal contraception, smoking, alcohol consumption, and psychosocial stress on the vaginal microbiota using next-generation sequencing. RESULTS: Based on our inclusion criteria, we incorporated 37 studies into this review. Hormonal contraception and personal hygiene were found to promote eubiosis of the vaginal microbiota. In contrast, sexual behaviors, smoking, alcohol consumption, and psychosocial stress were associated with an increased susceptibility to bacterial vaginosis, STIs, and severe pelvic inflammatory diseases due to a modified vaginal microbiota. Black ethnicity emerged as a confounding factor, with this population showing unstable vaginal microbiota. Oral contraception and a stable male sexual partner were found to favor Lactobacillus colonization, acting as a protective factor. Conversely, non-hormonal contraception and unprotected or non-penile/vaginal sexual activity increased the incidence of vaginal inflammation and bacterial vaginosis by disturbing the vaginal microbiota and reducing Lactobacillus abundance. CONCLUSION: Daily habits and lifestyle can influence the composition of the vaginal microbiota, thereby affecting vaginal health. Disturbances in the vaginal microbiota could be associated factors for STIs and vaginosis. Therefore, prioritizing more appropriate management of the vaginal microbiota is crucial.

Development of Norelgestromin Dissolving Bilayer Microarray Patches for Sustained Release of Hormonal Contraceptive.

Microarray patches (MAPs) offer a noninvasive and patient-friendly drug delivery method, suitable for self-administration, which is especially promising for low- and middle-income country settings. This study focuses on the development of dissolving bilayer MAPs loaded with norelgestromin (NGMN) as a first step towards developing a future potential drug delivery system for sustained hormonal contraception. The fabricated MAPs were designed with the appropriate needle lengths to penetrate the stratum corneum, while remaining minimally stimulating to dermal nociceptors. Ex vivo assessments showed that the MAPs delivered an average of 176 ± 60.9 µg of NGMN per MAP into excised neonatal porcine skin, representing 15.3 ± 5.3% of the loaded drug. In vivo pharmacokinetic analysis in Sprague Dawley rats demonstrated a Tmax of 4 h and a Cmax of 67.4 ± 20.1 ng/mL for the MAP-treated group, compared to a Tmax of 1 h and a Cmax of 700 ± 138 ng/mL for the intramuscular (IM) injection group, with a relative bioavailability of approximately 10% for the MAPs. The MAP-treated rats maintained plasma levels sufficient for therapeutic effects for up to 7 days after a single application. These results indicate the potential of NGMN-loaded dissolving bilayer MAPs, with further development focused on extending the release duration and improving bioavailability for prolonged contraceptive effects.