Utilization of clinical practice guidelines for cancer care in routine practice and during the coronavirus disease 2019 pandemic in India.

AIM: The coronavirus disease 2019 (COVID-19) pandemic affected cancer service delivery and the feasibility of following the standard treatment guidelines. The present paper describes the use of clinical care guidelines for cancer management in routine practice and the approach adopted towards cancer care during the COVID-19 pandemic in India. METHODS: A web-based survey was done in 107 hospitals (including public and private health facilities) that hosted Hospital-Based Cancer Registries under the National Cancer Registry Programme. The participants comprised Principal Investigators of these registries, who were also medical, surgical, and radiation oncology clinicians. The survey was done between May 1, 2021, and July 31, 2021. Participants were provided with a web link for the survey questionnaire, confidential login, and password. RESULTS: The study found high utilization of Clinical Practice Guidelines (CPGs) during practice, with eight out of ten physicians constantly to referring them. The study reported lack of knowledge, skills, and training to administer the treatment based on the guidelines followed by organizational infrastructure and affordability of treatment by the patients as the factors hampering utilization. International clinical guidelines were preferred when compared to national guidelines. The COVID-19 pandemic decreased the use of CPGs, wherein six out of ten clinicians reported their use. CONCLUSION: Stakeholders who formulate clinical guidelines must consider the practical aspects and feasibility of implementing such guidelines during a pandemic and similar situations. This should be coupled with adequate changes in care practice to ensure optimal care delivery and a continuum of cancer care in routine and pandemic-imposed situations.

Assessing the Global Impact of Ambient Air Pollution on Cancer Incidence and Mortality: A Comprehensive Meta-Analysis.

PURPOSE: This study aims to examine the association between exposure to major ambient air pollutants and the incidence and mortality of lung cancer and some nonlung cancers. METHODS: This meta-analysis used PubMed and EMBASE databases to access published studies that met the eligibility criteria. Primary analysis investigated the association between exposure to air pollutants and cancer incidence and mortality. Study quality was assessed using the Newcastle Ottawa Scale. Meta-analysis was conducted using R software. RESULTS: The meta-analysis included 61 studies, of which 53 were cohort studies and eight were case-control studies. Particulate matter 2.5 mm or less in diameter (PM2.5) was the exposure pollutant in half (55.5%), and lung cancer was the most frequently studied cancer in 59% of the studies. A pooled analysis of exposure reported in cohort and case-control studies and cancer incidence demonstrated a significant relationship (relative risk [RR], 1.04 [95% CI, 1.02 to 1.05]; I2, 88.93%; P < .05). A significant association was observed between exposure to pollutants such as PM2.5 (RR, 1.08 [95% CI, 1.04 to 1.12]; I2, 68.52%) and nitrogen dioxide (NO2) (RR, 1.03 [95% CI, 1.01 to 1.05]; I2, 73.52%) and lung cancer incidence. The relationship between exposure to the air pollutants and cancer mortality demonstrated a significant relationship (RR, 1.08 [95% CI, 1.07 to 1.10]; I2, 94.77%; P < .001). Among the four pollutants, PM2.5 (RR, 1.15 [95% CI, 1.08 to 1.22]; I2, 95.33%) and NO2 (RR, 1.05 [95% CI, 1.02 to 1.08]; I2, 89.98%) were associated with lung cancer mortality. CONCLUSION: The study confirms the association between air pollution exposure and lung cancer incidence and mortality. The meta-analysis results could contribute to community cancer prevention and diagnosis and help inform stakeholders and policymakers in decision making.

Profile of Childhood Cancers From Hospital-Based Cancer Registries in India, 2012-19.

OBJECTIVE: To describe the clinical pattern of childhood and adolescent cancers across India using hospital-based data in the National Cancer Registry Program. METHODS: Records of 60720 cancer cases in the 0-19 year age group for the period 2012-2019 from 96 hospital-based cancer registries were reviewed. Childhood cancers were classified based on the International Classification of Childhood Cancer (ICCC). Descriptive analysis was used to examine the distribution of cancer by five-year age groups, sex and ICCC diagnostic groups and subgroups. Data were analysed using IBM SPSS software and visualised using R software. RESULTS: 3.2% and 4.6% of all cancer cases in India were among children in the 0-14 year and 0-19 year age groups respectively. The male-to-female ratio for all cancers was 1.72 for 0-14 years and 1.73 for 0-19 years. The four leading groups of cancers among 0-14 year olds were leukemia (40%), lymphoma (12%), central nervous system tumor (11%) and bone cancer (8%). The four leading cancers among the 0-19 year age group were leukemia (36%), lymphoma (12%), bone (11%) and central nervous system tumor (10%). CONCLUSION: Cancers in the 0-14 and 0-19 age groups accounted for a considerable proportion of all cancers with significant male preponderance. Such information helps to fine-tune research and planning strategies.

An assessment of childhood cancer care services in India - gaps, challenges and the way forward.

Background: Childhood cancers are emerging as an essential concern in India where there is lack of a specific programme component or policy to address childhood cancer control. There is limited information on the status and quality of childhood cancer care services in India. This paper describes the childhood cancer care services available at secondary and tertiary-level hospitals in India through a cross sectional study design. Methods: The survey was conducted in 137 tertiary-level and 92 secondary-level hospitals in 26 states and 4 Union Territories (UTs), ensuring a uniform representation of public and private care hospitals. The study tool collected data on the organisational infrastructure, type of oncology services, health workforce, equipment, treatment and referral protocols, and treatment guidelines. Descriptive statistics was used to primarily present the health service status and data on childhood cancer care services in proportions and mean. Findings: A dedicated pediatric oncology department was available in 41.6% of the public, 48.6% of private, and 64% Non Government Organization (NGO) managed tertiary-level hospitals. In 36 (39%) of the 92 hospitals providing secondary care, childhood cancer care was provided. The availability of bone (41.5%) and positron emission tomography (PET) scans (25.9%) was lower in public tertiary hospitals, whereas histopathology, computerised tomography (CT scan), and magnetic resonance imaging (MRI) were lower in public secondary hospitals than private and NGO managed hospitals for the corresponding level of care. Most tertiary hospitals had the required supportive care facilities except for play therapy and hospice care. Less than 50% of the public tertiary hospitals had stocks of the four categories of cancer-treating drugs and essential infrastructure for radiotherapy and chemotherapy. Most secondary-level hospitals not treating childhood cancer had referral linkages with tertiary hospitals. Interpretation: The situational analysis of childhood cancer care services in India showed the concentration of availability of childhood cancer care services at the tertiary level of health care. There were gaps in the availability of specialised pediatric oncology care in all the tertiary hospitals. The availability of childhood cancer care services was higher in private and NGO-managed hospitals than in public hospitals. Integration of childhood cancer as a part of the national cancer control response should be taken up as a matter of priority. The need of the hour is to formulate a childhood cancer policy that will enable timely access to care universally. Funding: World Health Organization, India provided funding and technical support.

Need for accelerating tobacco control in India: findings from the national cancer registry programme.

OBJECTIVE: To describe the epidemiology of cancer in sites associated with tobacco use in India, according to recent findings from the National Cancer Registry Programme. METHODS: The data on cancers in sites associated with tobacco use has been sourced from 28 population-based and 58 hospital-based cancer registries of the National Cancer Registry Programme in India. The data covering a period of 5 years (2012-2016) was taken up for analysis. RESULTS: The highest age-adjusted incidence rate (AAR) among males was reported in the Aizawl district in Mizoram (197.3 per 100 000). The AAR was the highest (121.1 per 100 000) in the Papumpare district in females. The top five leading sites were cancers of the lung (10.7%), mouth (8.7%), oesophagus (6%), tongue (6%) and stomach (5%) among males and cancer of the cervix (10.3%), lung (4.3%), oesophagus (3.3%), mouth (3.3%) and tongue (2.7%) in females. The highest significant increase in AAR, indicated by the annual percentage change was seen among males in Aurangabad (3.4) and females in Kamrup urban (2.4). Except for lung cancer, most patients with other cancer types among both genders presented to the health facility with a locoregional (spread to nearby lymph nodes) disease spread. It is projected that in 2025, there will be 694367 cases of cancers in the sites associated with tobacco use. CONCLUSION: Tobacco uses in either form and cancer in sites associated with tobacco use are an important matter of public health concern in India. Cancer registries play a crucial role in identifying populations with high cancer incidence in sites associated with tobacco use, monitoring the trends over time, and evaluating the impact of tobacco control measures.

A rapid assessment of the impact of coronavirus disease (COVID- 19) pandemic on health care & service delivery for noncommunicable diseases in India.

BACKGROUND AND AIM: The coronavirus disease (COVID-19) pandemic had disrupted the availability, access and utilisation of routine health care services. The present study aimed to assess the impact of COVID-19 pandemic restrictions on India's Non communicable Disease (NCD) health care service delivery. METHODS: The study included existing hospitals in disease registry network of the Indian Council of Medical Research-National Centre for Disease Informatics and Research (ICMR-NCDIR), Bengaluru. The study participants comprised site investigators who were clinicians from many specialities, including general medicine, surgery, cancer, neurology, cardiology, and endocrinology. A standardised questionnaire was prepared to collect data on NCD health care services at the respective hospitals over three months from March to May 2020. RESULTS: Out of 153 hospitals approached for the study, 106 (70%) agreed to participate. Of these, 16 hospitals fully converted for COVID-19 care were excluded from the study. Thus, data from 90 hospitals were included in the final analysis. There had been a total disruption of NCD-related healthcare services during the three months in 44% of the hospitals. In April 2020, the outpatient attendance for over one-third of the hospitals was reduced by more than 75%. Admissions for planned surgeries for cancer treatment were reduced by more than 75% for about 40% of the hospitals. Preventive activities and population-based screening for diabetes, hypertension and cancer appear to have been adversely affected, with about one-third of the hospitals reporting total disruption in April and May 2020. As many as 60% of the institutions reported adequate availability of doctors. Over 91% of the institutions had preparedness/action plans to ensure the continuity of NCD services. CONCLUSION: The study shows that despite adequate human and material resources, NCD outpatient services, elective surgeries and population-based screening were severely affected. Most institutions were prepared to overcome the pandemic-imposed disruption and ensure a continuum of care for NCDs'.

Women cancers in India: Incidence, trends and their clinical extent from the National Cancer Registry Programme.

BACKGROUND: To provide a comprehensive assessment of women cancer in India utilizing the systematically collected data on all cancers by the National Cancer Registry Programme (NCRP). METHODS: The study examined 10,2287 cancer cases among women cancers providing cancer burden for major anatomical sites. Aggregated data of 28 PBCRs and 58 HBCRs under NCRP for 2012-16 was analysed for incidence rates, trends, cumulative risk of developing cancer, stage at detection and treatments offered. RESULTS: Study results have found region -wide variation of women cancers by indicating highest proportions in western followed by southern region of India. North-Eastern region had lowest proportion. It was observed that breast is highest ranking cancer in most registry areas of urban agglomerations of country while cancer cervix was leading site in registries of rural areas like Barshi (15.3) and Osmanabad &Beed (13.1). States of Mizoram (23.2) and Tripura (9.5) along with Pasighat, Cachar and Nagaland. Median age of occurrence for women for these anatomical sites ranged from 45 to 60 years of age. For cancer breast, cervix and ovary -most cases were detected with regional spread. These findings were different for cancer corpus uteri where registries have reported higher proportions (49.3 %) of localized stage at detection. Loco regional cancers had higher proportions of multimodality treatments. CONCLUSION: Study provides a foundation for assessing the status of women cancers in the country. Variations between geographies would guide appropriate support for action to strengthen efforts to improve cancer prevention and control in underserved areas of the country. This would facilitate advocacy for better investments and research on women cancers.

A clinicoepidemiological profile of lung cancers in India - Results from the National Cancer Registry Programme.

Background & objectives: Lung cancer is a significant public health concern in low- and middle-income countries such as India. The present article describes the epidemiology, and clinical profile of lung cancer in India, based on recent data from the National Cancer Registry Programme (NCRP). Methods: The latest data on lung cancer from the NCRP were collated from 28 population-based cancer registries and 58 hospital-based cancer registries across a five-year (2012-2016) reporting period. Results: The highest age-adjusted incidence rate and mortality (AAMR) was found amongst males and females in the Aizawl district of Mizoram. A significant increase in the annual per cent change of lung cancer incidence was observed in metropolitan cities from 1982 to 2016. About one-third of the cases (36.5%) in males and females (31.7%) were recorded in the age group of 55-64 yr. Adenocarcinoma accounted for about a third (34.3%) of the morphological type in males and half (52.7% ) amongst females. Out of 22,645 recorded lung cancer cases, close to half (44.8%) of the patients presented with distant spread, while over one-third (35.3%) had loco-regional spread of disease at the time of diagnosis. Interpretation & conclusions: Our estimates suggest that the number of cases is expected to rise sharply to 81,219 cases amongst males and 30,109 in females in 2025. The rising incidence and delayed diagnosis of lung cancer in India are grave concerns. The findings of the present study call for scaling up and intensification of lung cancer-specific preventive, early diagnosis and control measures.

Adolescent and young adult cancers in India-Findings from the National Cancer Registry Programme.

BACKGROUND: The adolescent and young adult (AYA) age group is a bridge between pediatric and adult age groups. The present study describes the epidemiology of cancers in the AYA age group in India. METHODS: The data of primary site cancers in the age group of 15-39 years from the 28 Population Based Cancer Registries (PBCRs') and 58 Hospital Based Cancer Registries under the National Cancer Registry Programme for the reporting year 2012-2016 was analysed. RESULTS: The median age adjusted incidence rate (AAR) was 22.2 per 100,000 among males and 29.2 per 100,000 among females. The age-specific incidence rate increased with increasing age in both genders with the highest recorded numbers in the 35-39 age group. The proportion of myeloid leukaemia and non-Hodgkin's lymphoma was highest in the 15-24 age group. Cancers of the breast, thyroid, mouth and tongue constituted the leading sites between 30 and 39 years. There was a significant increase in the incidence among AYA males (APC=0.9) between 1985 and 2015, while a decline in incidence was observed for females, which was not significant (APC=-0.2). The majority of patients had locoregional spread of cancer at the time of diagnosis. The projected number of cancer cases in both genders are expected to increase to 178,617 in 2025. CONCLUSION: Cancers in the AYA population are a concern in India. Since AYA oncology appears to be evolving in India, a robust health care system and suitable AYA cancer care policies and programmes are strongly needed to improve disease outcomes and survival.

Telemedicine and cancer care in India: promises, opportunities and caveats.

Telemedicine has revolutionized areas of medical practice and care. It has a potential in field of continuum of cancer care in India. SARS-CoV-2 has highlighted the potential use of this tool effectively. Scope of newer applications of telemedicine in field of cancer is reviewed in current paper enlisting benefits to patient, healthcare providers and centers in a developing country like India. Each of them is supported by appropriate evidence and examples. An analysis of strengths and opportunities when compared with weakness and threats brings out how telemedicine can redistribute oncology work force in a rational way and minimize disruption caused by the pandemic. Telemedicine can be utilized in cancer management starting from prevention, screening, diagnosis, treatment and rehabilitation to palliative care.

Specialists working for decades in the field of oncology are the best persons to endorse telemedicine, as they can leverage its use to its full potential. The present article is a rigorous review of past literature on telemedicine as well as proposed uses of technologies based on experiences of the authors. It will strengthen promotive, preventive, curative and rehabilitative healthcare delivery.

Strengthening Cancer Surveillance in India: Role of the National Cancer Registry Programme.

Cancer registries are an integral part of cancer surveillance and play a vital role in collecting and managing surveillance data. The National Cancer Registry Programme in India, which has been functional since 1981, has a wide network of 269 hospital-based and 38 population-based cancer registries functioning throughout the country. Cancer registries monitor and describe the trends in cancer incidence and mortality over time. They also provide vital information on the cancer caseload, such as the number of cancer patients in a specified location or the number of patients availing of care at a specific hospital. As a part of cancer surveillance, registries also play a critical role in designing cancer control plans, gauging the impact of primary and secondary preventive measures, and strengthening health systems. The data on cancer incidence have provided critical inputs to the central, state, and local government to plan, prioritize, and mobilize health resources for cancer control interventions. The role of cancer registries as a surveillance tool could be further strengthened by long-term sustainability through strong political will, making cancer a notifiable disease to facilitate reporting and linking cancer registries with medical records for better data capture.

Evaluation of a community-based HIV preventive intervention for female sex workers in rural areas of Karnataka State, south India.

To examine changes in behavioral outcomes among rural female sex workers (FSWs) involved in a community-based comprehensive HIV preventive intervention program in south India. A total of 14, 284 rural FSWs were reached by means of a community-based model for delivering outreach, medical, and referral services. Changes in behavior were assessed using 2 rounds of polling booth surveys conducted in 2008 and 2011. In all, 95% of the mapped FSWs were reached at least once, 80.3% received condoms as per need, and 71% received health services for sexually transmitted infections. There was a significant increase in condom use (from 60.4% to 72.4%, P = .001) and utilization of HIV counseling and testing services (from 63.9% to 92.4%; P = .000) between the 2 time periods. This model for a community-based rural outreach and HIV care was effective and could also be applied to many other health problems.

Characteristics and metabolic effects of estrogen and progestins contained in oral contraceptive pills.

Estrogen and progestins have been used by millions of women as effective combined oral contraceptives. Oral contraceptives (OCs) modify surrogate markers such as lipoproteins, insulin response to glucose, and coagulation factors, that have been associated with cardiovascular and venous risk. Ethinyl-Estradiol (EE) exerts a stronger effect that natural estradiol (E2) on hepatic metabolism. New progestins with high specificity have been designed to avoid interaction with other receptors and prevent androgenic, estrogenic or glucocorticoid related side-effects. The risks and benefits of new progestins used in contraception depend upon their molecular structure, the type and dose of associated estrogen, and the delivery route. The lower impact of E2-based combinations on metabolic surrogate markers may result in an improved safety profile, but only clinical outcomes are relevant to assess the risk. Large surveillance studies are warranted to confirm this hypothesis.

Contraception technology: past, present and future.

Steady progress in contraception research has been achieved over the past 50 years. Hormonal and nonhormonal modern contraceptives have improved women's lives by reducing different health conditions that contributed to considerable morbidity. However, the contraceptives available today are not suitable to all users, and the need to expand contraceptive choices still exists. Novel products such as new implants, contraceptive vaginal rings, transdermal patches and newer combinations of oral contraceptives have recently been introduced in family planning programs, and hormonal contraception is widely used for spacing and limiting births. Concerns over the adverse effects of hormonal contraceptives have led to research and development of new combinations with improved metabolic profile. Recent developments include use of natural compounds such as estradiol and estradiol valerate with the hope to decrease thrombotic risk, in combination with newer progestins derived from the progesterone structure or from spirolactone, in order to avoid the androgenic effects. Progesterone antagonists and progesterone receptor modulators are highly effective in blocking ovulation and preventing follicular rupture and are undergoing investigations in the form of oral pills and in semi-long-acting delivery systems. Future developments also include the combination of a contraceptive with an antiretroviral agent for dual contraception and protection against sexually transmitted diseases, to be used before intercourse or on demand, as well as for continuous use in dual-protection rings. Although clinical trials of male contraception have reflected promising results, limited involvement of industry in that area of research has decreased the likelihood of having a male method available in the current decade. Development of nonhormonal methods is still at an early stage of research, with the identification of specific targets within the reproductive system in ovaries and testes, as well as interactions between spermatozoa and ova. It is hoped that the introduction of new methods with additional health benefits would help women and couples with unmet needs to obtain access to a wider range of contraceptives with improved acceptability.

Effects of a novel estrogen-free, progesterone receptor modulator contraceptive vaginal ring on inhibition of ovulation, bleeding patterns and endometrium in normal women.

BACKGROUND: Progesterone receptor modulators (PRMs) delivered by contraceptive vaginal rings provide an opportunity for development of an estrogen-free contraceptive that does not require daily oral intake of steroids. The objective of this proof-of-concept study was to determine whether continuous delivery of 600-800 mcg of ulipristal acetate (UPA) from a contraceptive vaginal ring could achieve 80% to 90% inhibition of ovulation. STUDY DESIGN: This was a prospective, controlled, open-labeled, multicenter international trial to examine the effectiveness and safety of this prototype vaginal ring. Thirty-nine healthy women, 21-40 years old and not at risk of pregnancy, were enrolled at three clinic sites. Volunteers participated in a control cycle, a 12-week treatment period and a post-treatment cycle. Pharmacodynamic effects on follicular function and inhibition of ovulation, effects on endometrium, bleeding patterns and serum UPA levels were evaluated. RESULTS: Mean UPA levels during treatment were nearly constant, approximately 5.1 ng/mL throughout the study. Ovulation was documented in 32% of 111 "4-week treatment cycles." A correlation was observed between serum UPA and degree of inhibition of ovarian activity. There was no evidence of hyperplasia of endometrium, but PRM-associated endometrial changes were frequently observed (41%). CONCLUSION: In this study, the minimum effective contraceptive dose was not established. Further studies are required testing higher doses of UPA to attain ovulation suppression in a higher percentage of subjects.

Metabolic effects of contraceptive steroids.

Estrogen and progestins have been used by millions of women as effective combined contraceptives. The safety of hormonal contraceptives has been documented by years of follow-up and serious adverse events that may be related to their use are rare in the young population exposed to these agents. The balance between the benefits and the risks of contraceptive steroids is generally positive in particular when comparing to the risks of pregnancy and especially in women with risk factors. The metabolic changes induced by the synthetic steroids used in contraception, such as lipoprotein changes, insulin response to glucose, and coagulation factors have been considered as potential markers of cardiovascular and venous risk. Observations of these effects have led to modifications of the composition of hormonal contraceptive in order to minimize these changes and hence potentially decrease the risks. The synthetic estrogen Ethinyl-Estradiol (EE) exerts a stronger effect that natural estradiol (E2) on hepatic metabolism including estrogen-dependent markers such as liver proteins. This stronger hepatic impact of EE has been related to its 17α-ethinyl group which prevents the inactivation of the molecule and results in a more pronounced hepatic effect of EE as compared to estradiol. Due to its strong activity, administering EE via a non-oral route does not prevent its impact on liver proteins. In order to circumvent the metabolic changes induced by EE, newer products using more natural compounds such as estradiol (E2) and estradiol valerate (E2V) have been introduced. The synthetic progestins used for contraception are structurally related either to testosterone (T) (estranes and gonanes) or to progesterone (pregnanes and 19-norpregnanes). Several new progestins have been designed to bind more specifically to the progesterone receptor and to minimize side-effects related to androgenic, estrogenic or glucocorticoid receptor interactions. Dienogest (DNG), and drospirenone (DRSP) and the 19-norpregnanes including Nestorone® (NES), nomegestrol acetate (NOMAc) and trimegestone (TMG) have been combined with estrogen either EE or E2 or estradiol valerate (E2V). Risks and benefits of the newer progestins used in contraception depend upon the type of molecular structure, the type and dose of estrogen associated in a combination and the route of administration. The lower metabolic impact of estradiol-based combinations may result in an improved safety profile, but large surveillance studies are warranted to confirm this plausible hypothesis. So far, the contraindications and warnings for use of current COCs also apply to the estradiol-based COCs.

The use of newer progestins for contraception.

The synthetic progestins used for contraception so far are structurally related either to testosterone (estranes and gonanes) or to progesterone (pregnanes and 19-norpregnanes). Several new progestins have been designed to minimize side-effects related to androgenic, estrogenic or glucocorticoid receptor (GR) interactions. Dienogest (DNG) and drospirenone (DRSP) exhibit a partial antiandrogenic action, and DRSP has predominant anti-mineralocorticoid properties. The 19-norpregnanes include Nestorone (NES), nomegestrol acetate (NOMAc) and trimegestone (TMG), and possess a high specificity for binding to the progesterone receptor (PR) with no or little interaction with other steroid receptors. DRSP has been developed as combination oral pills with ethinyl estradiol (EE); DNG has been combined both with EE and, more recently, with estradiol valerate (E2V). NOMAc has been used as a progestin-only method and more recently combined with estradiol (E2). Nestorone is not active orally but proved to be the most active antiovulatory progestin when used parenterally. It has been developed in various formulations such as implants, vaginal rings or transdermal gel or spray. Risks and benefits of the new progestins depend upon the type of molecular structure, the type of estrogen associated in a combination and the route of administration.

Progesterone vaginal ring for contraceptive use during lactation.

The progesterone vaginal ring (PVR) has been shown to be effective as a contraceptive in breastfeeding women who need a better method of spacing pregnancies, and previous clinical trials of 1-year duration demonstrated its efficacy to be similar to that of the IUD during lactation. The duration of lactational amenorrhea is significantly prolonged in PVR users in comparison to IUD users with fewer median numbers of bleeding/spotting (B/S) episodes and B/S days. This long-acting delivery system designed for 3-month use needs to be renewed every 3 months as long as breastfeeding continues. The system designed as a matrix ring delivers 10 mg/day of the physiological hormone progesterone. Various factors such as comfort, ease of use, user control, rather than provider-dependent, and the fact that it contains a natural hormone have contributed to a high acceptability of the PVR method by breastfeeding women. The frequency of breastfeeding, breast milk volume and infant growth were not different in PVR users or IUD users, and the safety of this new method has been well documented. This article describes the available information and the results of the studies that led to approval of this method in several countries in Latin America so far. Further evaluation of the PVR acceptability in different populations where breastfeeding is popular and highly recommended for the infant's benefit is warranted.

Intrauterine administration of CDB-2914 (Ulipristal) suppresses the endometrium of rhesus macaques.

BACKGROUND: Ulipristal (UPA; CDB-2914) is a progesterone receptor modulator with contraceptive potential. To test its effects when delivered by an intrauterine system (IUS), we prepared control and UPA-filled IUS and evaluated their effects in rhesus macaques. STUDY DESIGN: Short lengths of Silastic tubing either empty (n=3) or containing UPA (n=5) were inserted into the uteri of 8 ovariectomized macaques. Animals were cycled by sequential treatment with estradiol and progesterone. After 3.5 cycles, the uterus was removed. RESULTS: During treatment, animals with an empty IUS menstruated for a mean total of 11.66+/-0.88 days, while UPA-IUS treated animals bled for only 1+/-0.45 days. Indices of endometrial proliferation were significantly reduced by UPA-IUS treatment. The UPA exposed endometria were atrophied with some glandular cysts while the blank controls displayed a proliferative morphology without cysts. Androgen receptors were more intensely stained in the glands of the UPA-IUS treated endometria than in the blank-IUS treated controls. CONCLUSIONS: In rhesus macaques, a UPA-IUS induced endometrial atrophy and amenorrhea. The work provides proof of principle that an IUS can deliver effective intrauterine concentrations of Ulipristal.

Parenteral administration of progestins for hormonal replacement therapy.

New options for hormonal replacement therapy (HRT) include non-oral, low-dose sustained delivery of progestins in different formulations. Since the Women's Health Initiative (WHI) study, prescription trends were observed selecting progesterone over other progestins, or delivering the progestin parenterally, in order to reach low systemic levels of the steroid. Such modalities include progesterone vaginal rings or gels, and intra-uterine systems (IUSs). When given via the transdermal and intranasal routes, the hormones are delivered systemically although the first liver impact is by-passed. Of the progestins selected for delivery of low doses by means of an IUS, or transdermally, only very active molecules can be used. An IUS approved for HRT in several countries delivers very low doses of levonorgestrel (LNG) in the uterine cavity. Nestorone is well absorbed transdermally from a gel as well as from a metered dose transdermal system (MTDS) that sprays an invisible film on the skin. Transdermal patches combining oestradiol with either norethisterone acetate or LNG have been available for several years. Although parenteral administration of progesterone or low-dose progestins should in theory be associated with fewer side-effects than oral therapy, the long-term safety of the newer systems warrants further evaluation.