Isaac Manyonda

Women's sexual health after childbirth

Objective To investigate the impact of childbirth on the sexual health of primiparous women and identify factors associated with dyspareunia.

Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia

Pre-eclampsia is a principal cause of maternal morbidity and mortality, affecting 5–10% of first pregnancies worldwide. Manifestations include increased blood pressure, proteinuria, coagulopathy and peripheral and cerebral oedema. Although the aetiology and pathogenesis remain to be elucidated, the placenta is undoubtedly involved, as termination of pregnancy eradicates the disease. Here we have cloned a complementary DNA from human placental messenger RNA encoding a precursor protein of 121 amino acids which gives rise to a mature peptide identical to the neuropeptide neurokinin B (NKB) of other mammalian species. In female rats, concentrations of NKB several-fold above that of an animal 20 days into pregnancy caused substantial pressor activity. In human pregnancy, the expression of NKB was confined to the outer syncytiotrophoblast of the placenta, significant concentrations of NKB could be detected in plasma as early as week 9, and plasma concentrations of NKB were grossly elevated in pregnancy-induced hypertension and pre-eclampsia. We conclude that elevated levels of NKB in early pregnancy may be an indicator of hypertension and pre-eclampsia, and that treatment with certain neurokinin receptor antagonists may be useful in alleviating the symptoms.

Characterization of the endokinins: Human tachykinins with cardiovascular activity

We report four human tachykinins, endokinins A, B, C, and D (EKA–D), encoded from a single tachykinin precursor 4 gene that generates four mRNAs (α, β, γ, and δ). Tachykinin 4 gene expression was detected primarily in adrenal gland and in the placenta, where, like neurokinin B, significant amounts of EKB-like immunoreactivity were detected. EKA/B 10-mers displayed equivalent affinity for the three tachykinin receptors as substance P (SP), whereas a 32-mer N-terminal extended form of EKB was significantly more potent than EKA/B or SP. EKC/D, which possess a previously uncharacterized tachykinin motif, FQGLL-NH2, displayed low potency. EKA/B displayed identical hemodynamic effects to SP in rats, causing short-lived falls in mean arterial blood pressure associated with tachycardia, mesenteric vasoconstriction, and marked hindquarter vasodilatation. Thus, EKA/B could be the endocrine/paracrine agonists at peripheral SP receptors and there may be as yet an unidentified receptor(s) for EKC/D.

CLINICAL PRESENTATION OF FIBROIDS

Uterine fibroids, the most common tumours in women of reproductive age, are asymptomatic in at least 50% of afflicted women. However, in other women, they cause significant morbidity and affect quality of life. Clinically, they present with a variety of symptoms: menstrual disturbances including menorrhagia, dysmenorrhoea and intermenstrual bleeding; pelvic pain unrelated to menstruation; and pressure symptoms such as a sensation of bloatedness, increased urinary frequency and bowel disturbance. In addition, they may compromise reproductive function, possibly contributing to subfertility, early pregnancy loss and later pregnancy complications such as pain, preterm labour, malpresentations, increased need for caesarean section, and postpartum haemorrhage. Large fibroids may distend the abdomen, which may be aesthetically displeasing to many women. Abnormal bleeding occurs in 30% of symptomatic women, and abnormal bleeding, bloating and pelvic discomfort due to mass effect constitute the most common symptoms. The incidence of fibroids is highest in Black women, who tend to have multiple and larger fibroids, and more symptomatic fibroids at the time of diagnosis. The prevalence of clinically significant myomas peaks in the perimenopausal years and declines after the menopause. It is not known why some fibroids are symptomatic while others are quiescent. The size, number and location of fibroids undoubtedly determine their clinical behaviour, but research has yet to correlate these parameters with clinical presentation of the fibroids.

Medical management of fibroids

The ideal medical therapy for fibroids is, arguably, a tablet that is taken by mouth, once a day or, even better, once a week, with minimal, if any, side-effects, that induces fibroid regression and thus a resolution of symptoms rapidly, but without affecting fertility. Such a magic bullet does not yet exist, and there are no indications that one is on the horizon. Driven by the observation that fibroid growth is hormone dependent, current medical treatments mainly involve hormonal manipulations. Gonadotrophin-releasing hormone analogues (GnRHa) have been the most widely used, and while they do cause fibroid regression, they can only be used in the short term, as temporizing measures in the perimenopausal woman, or pre-operatively to reduce fibroid size, influence the type of surgery, restore haemoglobin levels and apparently reduce blood loss at operation. They are notorious for rebound growth of the fibroids upon cessation of therapy, and have major side-effects. GnRH antagonists avoid the initial flare effect seen with GnRHa therapy, but otherwise do not appear to have any additional advantages over GnRHa. Selective oestrogen receptor modulators, such as raloxifene, have been shown to induce fibroid regression effectively in post-, but not pre-, menopausal women; even in the former group, experience with these drugs is limited, and they are associated with significant side-effects. Aromatase inhibitors only appear to be effective in postmenopausal women, have potentially significant long-term side-effects, and experience with their use is also limited. There are suggestions that the levonorgestrel intra-uterine system can cause dramatic reduction in menstrual flow in women with fibroids, but to date there have been no RCTs of its use in these women, in whom rates of expulsion of the device appear to be high. The progesterone antagonists mifepristone and asoprisnil have shown significant promise and warrant further research, as they appear to show efficacy in inducing fibroid regression without major side-effects. However, they and the other hormonal therapies that alter oestrogen and progesterone production or function significantly (danazol, gestrinone) are not compatible with reproduction. Therefore, the quest for the ideal medical therapy for fibroid disease continues, and increasing understanding of fibroid biology is ushering in non-hormonal therapies, although all are confined to laboratory experimentation at present. In the meantime, surgical and radiological approaches remain the mainstay effective therapies.

Bladder, bowel and sexual function after hysterectomy for benign conditions

Approximately 28 per 10,000 women undergo hysterectomy every year, rendering it the commonest major gynaecological operation in the UK’. The procedure disrupts the intimate anatomical relationship between the uterus, bowel, bladder and vagina, and inevitably the local nerve supply. It is therefore reasonable to suppose that hysterectomy might alter their function, such change being either detrimental or beneficial. Since Hanley’s2 work in the late 1960s, there has been an increasing awareness of and research into the sequelae of hysterectomy. The procedure may be total, when both the body of the uterus and the cervix are removed, or subtotal, when the cervix is conserved. The operation may be performed via an abdominal incision, or by the vaginal route, or more recently by minimal access techniques. If hysterectomy does indeed affect urinary, bowel or sexual function, the type and route of the operation may also affect the degree of change. This article reviews current literature on this topic.

Hysterectomy improves quality of life and decreases psychiatric symptoms: a prospective and randomised comparison of total versus subtotal hysterectomy

Objective  To conduct a prospective and concurrent evaluation of changes in health status and quality of life and psychological outcome measures over one year in women randomised to total or subtotal abdominal hysterectomy. The concurrent evaluation was the impact of total versus subtotal hysterectomy on bladder, bowel and sexual function.

Controversies and challenges in the modern management of uterine fibroids

Uterine fibroids are the most common tumour in women during the reproductive years, occurring in an estimated 20–50% of women over the age of 30 years, increasing with age and being more common in certain ethnic populations, especially the Afro-Caribbean. They have a major impact on women’s health, being the most common indication for hysterectomy in England in 1993–1994, while in the United States by the age of 60 years, 30% of women will have had a hysterectomy, of which 60% will have been performed to treat fibroids. Fibroids therefore have a significant cost implication, the 72,362 hysterectomies performed for fibroids in 1993–1994 costing the NHS an estimated £70 million. While there is no disputing that fibroids can cause menorrhagia, pelvic pain/discomfort and bladder and bowel compression symptoms, at least 50% remain asymptomatic, and it is uncertain whether they impair fertility or cause miscarriage. While myomectomy and hysterectomy are the mainstay treatment modalities, there are major uncertainties and controversies on optimal therapy and standard clinical outcome measures. The place of newer treatments such as uterine artery embolisation (UAE), laparoscopic and vaginal myomectomy has yet to be evaluated.

WOMEN'S SEXUALITY AFTER CHILDBIRTH : A PILOT STUDY

A pilot study was carried out investigatingwomens sexual health in the postnatal period. Postalquestionnaires were sent to a cohort of 158 primiparouswomen approximately 7 months after delivery. Women who had resumed sexual intercourse were askeda detailed set of questions about problems experienced,sexual practices, frequency of intercourse, satisfactionwith sex life, and consultation for postnatal sexual problems. All women were asked about theinformation they received on postnatalhealth prior tothe birth and any information or help and advice theyreceived from health professionals on the subject after the birth. Ninety-eight women (62%)responded. Women experienced significant levels ofmorbidity in the postnatal period; 3 months afterdelivery 58% experienced dyspareunia, 39% experiencedvaginal dryness, and 44% suffered loss of sexualdesire. These figures had reduced to 26, 22, and 35%,respectively, by the time of answering the questionnaire(approximately 8 to 9 months after delivery). Compared to before pregnancy, there was a decrease infrequency and satisfaction with sexual intercourse,although sexual practices changed little. Of the 67women who reported a postnatal sexual problem, only 19% discussed this with a health professional.Conversations with health professionals in routinepostnatal health contacts were mainly aboutcontraception, and only rarely discussed problems withintercourse.

A role for noradrenaline in pre‐eclampsia: towards a unifying hypothesis for the pathophysiology

Objective To compare plasma catecholamine (noradrenaline and adrenaline) levels in pre‐eclamptic to normotensive pregnancy, and to study the activity of synthetic enzymes for catecholamines in placental and trophoblastic cell cultures. We postulated that catecholamines might be an important signal secreted by the fetoplacental unit in pre‐eclampsia.