ROLE OF LEPTIN RESISTANCE IN OBESITY.

                                 

      Obesity is from the Latin word ‘obesitas’ which means stout, fat or plump. Obesity is a condition in which excess body fat or adipose tissue has accumulated to the extent that it may have an adverse effect on health. Obesity is one of the leading preventable causes of death worldwide, with increasing prevalence in adults and children.

   Obesity results from an imbalance of energy intake versus expenditure and a disturbance in the factors that regulate the feedback process. The causes are multifactorial and can be considered in terms of the bio-psychosocial model. That is, biological factors (genetic, metabolic factors, comorbidities, medications); psychological disturbances (eating disorders, activity habits, health knowledge); and social factors (socio-economic status, food policy etc) all intersect in obesity.

     Although there is no definitive answer to the pathophysiology of severe obesity, it is clear that a severely obese individual has, in general, persistent hunger that is not satisfied by amounts of food that satisfy the non-obese. This lack of satiety or maintenance of satiety may be the single most important factor in the process. Ongoing research has identified complex humoral and neural mechanisms that control appetite and satiety. These neurohumoral mechanisms respond to genetic, nutritional, environmental and psychological signals and trigger a metabolic response through stimulation of centres located in the hypothalamus. Leptin (which is a hormone synthesized by fat cells), ghrelin (hormone produced in the stomach and arcuate nucleus) and other appetite related hormones act on the hypothalamus.

     There are several circuits within the hypothalamus that contribute to its role in integrating appetite, the melanocortin pathway being the best understood. The circuit begins with an area of the hypothalamus, the arcuate nucleus that has output to the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH), the brain’s feeding and satiety centres respectively. The arcuate nucleus contains two distinct groups of neurons. The first group co-expresses neuropeptide Y (NPY) and agouti-related peptide (AgRP) and has stimulatory inputs to the LH and inhibitory inputs to the VMH. The second group co-expresses pro-opiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART) and has stimulatory inputs to the VMH and inhibitory inputs into the LH. Consequently, NPY/AgRP neurons stimulate feeding and inhibit satiety while POMC/CART stimulates satiety and inhibit feeding.

        Leptin inhibits NPY/AgRP group while stimulating the POMC/CART group. Therefore, deficiency of leptin or leptin resistance leads to overfeeding and may account for some genetic and acquired obesity.

      Other hormones that play role in metabolism and by extension obesity include adiponectin (a hormone produced by adipocytes), amylin, and insulin, PYY, amongst others. Adiponectin directs fatty acids to muscle for oxidation thereby decreasing fat mass. The levels of adiponectin in the blood are very high normally. The level of this hormone is lower in obese people than in lean individuals.

UTERINE FIBROID

                                                  UTERINE FIBROID

     

      Fibroids are benign tumour of the uterine smooth muscle. Fibroids are the commonest benign tumour of the female genital tract. It is estimated that about one-fifth of all women have fibroid present in the uterus at death. They are composed essentially of muscle tissue although there is also a variable amount of fibrous tissue. Fibroids are also called fibromyoma, fibroma or leiomyoma. They are frequently small and often multiple. The renowned Nigerian gynaecologist Professor Ajabor reported removing as many as 200 fibroids from one patient. Fibroids tend to be spherical but sometimes, the surface can be lobulated. They may grow to immense size and fill the entire abdomen. Although the rates of growth of myomas vary from one individual to another, fibroids are often slow growing. It is believed that at menopause, fibroids stops growing or some may get smaller but it is said that about 10% of myomas continue to grow even after the menopause. The vast majority of fibroids are asymptomatic and will not require any treatment but sometimes, fibroid may become symptomatic and require treatment varying from supportive measures to medical or surgical management.

      Several factors have been implicated in the aetiology of fibroids; one of which is the age of the individual. Fibroids are rare before the age of twenty and it is clinically detectable in about 20% of women over the age of thirty years. Another factor that may play a role is the parity of the woman. Myomas are more common in nulliparous women or women who are relatively infertile. Fibroids also show a racial tendency being more common amongst women of  African racial origin. Genetic factors have also being implicated in the pathogenesis of fibroid. Its prevalence in the reproductive years has made some authorities to speculate that ovarian hormone may also play a role in the genesis of fibroid. There is also some suggestion that it may be due to ovarian stimulation from oestrogen. Myomas can also be familial. Obesity is another recognized predisposing factor.

      A patient with uterine fibroid when not pregnant, may come to the hospital with menstrual disturbance like menorrhagia especially with the submucous type (i.e, fibroids bulging into the endometrial cavity) and anaemia may result from the menorrhagia. Some women may develop congestive or spasmodic dysmenorrhoea. Some patients may present with irregular vaginal bleeding and other vaginal discharge when the surface of the fibroid is ulcerated. Some patients may even present with a swollen abdomen and may have pressure symptoms fibroid like irritation of the bladder, retention of urine, and hydronephrosis from compression of the ureters if the fibroid is large enough. There may be referred pain on the limbs from pressure on the sacral nerves. There may be lymphatic obstruction giving rise to elephantiasis. When there is compression on the rectum, it may result in constipation. Fibroids especially when small and few will not usually be the reason why a woman will be infertile but larger ones may play a role. But coexisting fibroid may have effects on the current pregnancy. Fibroids may cause malposition and malpresentation of the developing foetus.  It may make the uterus appear larger than expected for date. When fibroids occupy the lower uterine segment, it may cause obstructed labour. Normally, fibroids are relatively avascular and acute disruptions of their blood supply during their active growth that ocuur in pregnancy may result in necrobiosis of the fibroid. This necrobiosis of the fibroid also referred to as red degeneration is frequently seen in pregnancy especially in the second trimester. The patient usually in the second trimester of pregnancy presents to the obstetrician with acute emergency abdominal pain and at times may require exploratory laparotomy. This red degeneration may be difficult to differentiate from torsion of a subserosal fibroid (that is, fibroids at the outer border of the myometrium). Fibroids especially the submucous and intramural type (fibroids that are centrally within the myometrium), can predispose to post partum haemorrhage from uterine atony.

     Apart from the red degeneration mentioned earlier, fibroids can under other degenerations irrespective of pregnancy. When fibroids gradually outgrow their blood supply, they undergo hyaline degeneration. There can also be calcification, myxomatous, mucocoele, cystic and rarely sarcomatous degeneration.

     On examination of a patient with fibroid, the tumour is usually but not always hard. It is usually rounded or lobulated; may be movable from side to side and usually one can get above it and not below it on palpation. Tenderness may be elicited if the tumour is undergoing red or sracomatous degenerative changes.

     Important differential diagnoses to consider in a woman with fibroid include adenomyosis of the uterus, enlarged gravid uterus, ovarian tumours and horn of a bicornuate uterus. 

    Investigations will include a pregnancy test to rule out pregnancy as a cause of abdominal distension and packed cell volume or haemoglobin concentration to detect anaemia if present due to bleeding. Imaging of the renal tract may be helpful in the presence of large fibroids to exclude hydronephrosis due to pressure of the mass on the ureters. Clinical suspicion of a sarcoma will be an indication for needle biopsy.

    Asymptomatic fibroids do not usually require any treatment. So, what is done is masterly inactivity. For those women of reproductive age who have symptoms and still want to maintain their conception potential, conservative myomectomy is done. Any important point for preoperative discussion is that there is a small but significant risk of uncontrolled bleeding during myomectomy, which could lead to the need for hysterectomy. For perimenopausal women who have completed their family size, total abdominal hysterectomy is done. Before hysterectomy or myomectomy, patients should be optimised, renal function should be assessed and blood should be available in case the need for transfusion arises. Hysterectomy and myomectomy can be facilitated by gonadotropin releasing hormone agonist pretreatment to reduce the bulk and vascularity of the fibroids before surgery.  While effective in shrinking fibroids, this medical management when used alone without surgery, the fibroids will grow again once the drugs are stopped.

    Other methods of treating fibroids include laparoscopic myomectomy, hysterectomy through a laparoscope, and arterial embolisation especially in patients with large fibroids who are unfit for more surgeries.

   In conclusion, uterine fibroids are common are common, and are usually asymptomatic but active management may become necessary when it impairs the patient’s function.

SOCIAL ISSUES: Young People and Family Planning: Teenage Pregnancy

                                    Young People and Family Planning: Teenage Pregnancy

                                          

DEFINITION

Teenage pregnancy is defined as a teenage girl, usually within the ages of 13-19, becoming pregnant.

The term in everyday speech usually refers to girls who have not reached legal adulthood, which varies across the world, who become pregnant.

THE CURRENT SITUATION

•     Half of the world’s population are under 25. Some 1.8 billion are aged 10-25, history’s largest generation of adolescents, and about 85% live in the developing world.

•       Most people become sexually active before their 20th birthday.

•       49% of girls in least developed countries marry before they turn 18.

•     10% – 40% of young unmarried girls have had an unintended pregnancy according to community studies.

•     Some 14 million children worldwide are born every year to young married and unmarried women aged 15 to 19.

•     According to the Nigerian Demographic and Health Survey by the National Population Commissio in 2008, the adolescent fertility rate in Nigeria, was 121 live births per 1,000 births, which as the highest in sub-Saharan Africa. According to the same survey, Katsina state has come out top as the state with the highest rate of teenage pregnancy and motherhood in Nigeria. Katsina state accounted for 65% of teenage pregnancy while Edo state recorded the least percentage of 2.9%. Furthermore, teenage pregnancy is higher in the northern geopolitical zone. One in every three girls in northern Nigeria has started childbearing in 2008, compared to one in every ten in the south.

•     Among the developed countries, the United States, United Kingdom and New Zealand have the highest level of teenage pregnancy while Japan and South Korea have the lowest in 2001 survey. The teenage birth rate in the United States is the highest in the developed world.

•     The highest rate of teenage pregnancy in the world is in sub-Saharan Africa, where women tend marry at an early age.

      CAUSES OF TEEN PREGNANCIES

Teen pregnancies may result for different reasons in industrialised countries as compared to developing countries. Factors that contribute to teenage pregnancies include:

•       Customs and traditions that lead to early marriage (developing countries)

•       Adolescent sexual behaviour which may also be influenced by alcohol and drugs especially ecstasy, cannabis and amphetamines. These drugs are inhibition-reducing.

•     Lack of education and information about reproductive sexual health including lack of access to tools that prevent pregnancies: adolescents may lack knowledge of or access to conventional methods of preventing pregnancy as they may be too embarrassed or frightened to seek such information.

•       Peer pressure to engage in sexual activity

•       Incorrect use of contraception

•       Sexual abuse that leads to rape: multiple studies have indicated a strong link between early childhood sexual abuse and subsequent teenage pregnancy in industrialized countries. Up to 70% of women who gave birth in their teens were molested as young girls.

•       Poverty: economically poor countries such as Niger and Bangladesh have far more teenage mothers compared with economically rich countries such as Switzerland and Japan.

•       Exposure to abuse, violence and family strife at home: women exposed to abuse, domestic violence and family strife in childhood are more likely to become pregnant as teenagers and the risk of becoming pregnant as a teenager increases with the number of adverse childhood experiences. According to a 2004 study, about one-third of teenage pregnancies could be prevented by eliminating exposure to abuse, violence and family strife. Foster care youths are more likely than their peers to become pregnant as teenagers.

•       Low self esteem

•       Low educational ambitions and goal.

•       Media influence: a study conducted in 2006, found that adolescents who were more exposed to sexuality in the media were also more likely to engage in sexual activities themselves.

TEEN PREGNANCY: LIFE OUTCOMES ON A TEEN MOTHER, HER CHILD AND SIBLINGS

Research indicates that teen pregnancy and motherhood can have detrimental socio economic and psychological outcomes for the teen mother, her child, and her young siblings.

a) A teen mother is more likely to:

•   drop out of school

•   have no or low qualifications

•   be unemployed or low-paid

•   live in poor housing conditions

•   suffer from depression which may result in suicide

•   live on welfare

b) The child of a teen mother is more likely to:

•   live in poverty

•   grow up without a father

•   become a victim of neglect or abuse

•   do less well at school

•   become involved in crime

•   abuse drugs and alcohol

•   eventually become a teenage parent and begin the cycle all over again

c) The younger sibling of a teen mother is more likely to:

•   accept sexual initiation and marriage at a younger age

•   place less importance on education and employment

TEEN PREGNANCY: MEDICAL OUTCOMES

•      Research indicates that pregnant teens are less likely to receive prenatal care, often seeking it only in the third trimester, if at all.

•      As a result of insufficient prenatal care, the global incidence of premature births and low birth weight is higher amongst teenage mothers.

•      Risks for medical complications are greater for girls 14 years of age and younger, as an underdeveloped pelvis can lead to difficulties in childbirth.

•   Young women under 20 face a higher risk of obstructed labour, which if Caesarean section is

not available can cause an obstetric fistula, a tear in the birth canal that creates leakage of urine and/or faeces. At least 2 million of the world’s poorest women live with fistulas.

•      Complications during pregnancy and delivery are the leading causes of death for girls aged 15 to 19 in developing countries. They are twice as likely to die in childbirth as women in their 20s.

•      Teenage girls account for 14% of the estimated 20 million unsafe abortions performed each year, which result in some 68,000 deaths.

TEEN PREGNANCY: STIs, HIV AND AIDS

•      As a result of unprotected sex, young people are also at risk of sexually transmitted diseases and HIV infection.

•      The highest rates of STIs worldwide are among young people aged 15 to 24. Some 500,000 become infected daily (excluding HIV).

•   Two in five new HIV infections globally occur in young people aged 15 to 24.

•      Surveys from 40 countries show that more than half their young people have misconceptions about how HIV is transmitted.

•      Married adolescent girls generally are unable to negotiate condom use or to refuse sexual relations. They are often married to older men with more sexual experience, which puts them at risk of contracting STIs, including HIV.

 PREVENTION OF TEENAGE PREGNANCY.

•       The Dutch approach to preventing teenage pregnancy has often been seen as model by other   countries. The curriculum focuses on values, attitudes, communication and negotiation skills as well as biological aspects of reproduction.

•       Some authors advocate better sex education and improving contraceptive and advice services for young people, supporting the parents of teenagers to talk to them about sex and relationships especially targeting the high-risk group.

•       Improved female literacy and educational prospects have led to an increase in the age at first birth.

•       Laws against child marriage.

•       Endorsing beliefs that support safe sex practices

•       Improved security

•       Clinicians and parents should be non-judgemental when approached for advice regarding sex issues.

                          

   WORLD RECORD

 Though not a teenager, Lina Medina of Peru, holds the world record for the youngest live birth; she was 5 years, 7 months old when she gave birth.

Sources:

The Lancet’s Maternal Survival and Women Deliver Series (2006/2007);

2005 World Health Report

2001 Innocenti Report: League Table of Teenage Births in Rich Nations

UNFPA Resource Kit: World Population Day 2008

Wikipedia.

American academy of paediatrics.

Wikihow.