Anita Nath

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.

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.

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.

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 infants 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.

Adolescent friendly health services in India: A need of the hour.

Adolescents account for almost one third of Indias population. They are prone to suffer from reproductive and sexual health, nutritional, mental and behavioral problems. Health services which cater exclusively to the needs of adolescents are scanty and concentrated in urban areas. Adolescent Friendly Health Services (AFHS) which provide a broad range of preventive, promotive and curative services under one roof can help to ensure improved availability, accessibility and utilization of health services. AFHS is being initiated by governmental, private and non-governmental organizations. Lessons to improve the quality of AFHS could be further learnt from evaluation of pilot projects and success stories of similar initiatives in other countries.

A Qualitative Evaluation of the Information, Education, and Communication Component of the Tuberculosis Control Program in Delhi, India

Tuberculosis control programs have recognized and addressed those system components in which knowledge and behavior of the patient and the general population are key issues because they have a profound influence on the treatment-seeking behavior and completion of course of treatment. As a part of the Revised National Tuberculosis Control Program, the ongoing information, education, and communication (IEC) efforts in Delhi were further intensified in the form of a multipronged media campaign. The objectives of this study are to evaluate (a) the impact of the campaign on awareness generation among the target audiences, (b) their opinion for making the campaign more effective and suited to their needs, and (c) perceptions of health personnel regarding the campaign. The study follows a descriptive cross-sectional design. The following qualitative methods were used: (a) focus group discussions of patients and the general population, (b) 3 key informant interviews of the health care personnel and a defaulter patient, and (c) in-depth interviews of 20 DOTS (directly observed treatment, short course) providers. The study observed that (a) different sociocultural segments of the population varied in terms of their observations of IEC messages, (b) stigma associated with tuberculosis is widely prevalent despite having a campaign, and ( c) television was voted as the most effective IEC medium. IEC strategies should be tailor-made and suited to the needs of a particular subpopulation.

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 Womens 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.

HIV/AIDS and Indian youth – a review of the literature (1980 - 2008)

The main objective of this article is to provide a comprehensive overview of the situation regarding HIV/AIDS among youth in India, and explore the possible strategies that could be effective in combating the spread of this disease. India is in the grip of the HIV/AIDS epidemic, with an increasing number of infections being reported among youth, who comprise a quarter of the population but account for almost one-third of the HIV/AIDS burden. The prevalence in young women appears to be on the rise. Although the majority of youth are aware of the disease, a number of myths and misconceptions still prevail. Furthermore, or as a consequence, a higher percentage of young males report engaging in premarital sexual activity compared with females. Even though condom awareness is fairly high, condom usage is low. Of late, sex tourism and its implications for the HIV/AIDS epidemic present an increasing concern. Indian youth appear to hold negative attitudes towards HIV testing and people living with HIV/AIDS. Although a number of preventive and control programmes and policies exist, these need further strengthening and evaluation.

Applying emerging science to contraception research: implications for the clinic

Emerging science will make an important contribution towards the development of improved contraceptives. While long-acting reversible contraceptives remain the most effective method, new user-controlled, mid-acting methods will avoid the need for procedures requiring trained providers. Contraceptives combined with other agents may bring additional health benefits, such as dual protection against both pregnancy and sexually transmitted infections. Emerging research areas in proteomics allowed the discovery of new reproductive targets that may lead to non-hormonal contraceptives for both men and women. Current research objectives include the improvement of existing contraceptive methods, as well as discovery of new materials able to deliver new molecules more specifically to their target without systemic actions.