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Hypertension is one of many side effects of oral contraceptive use in a small percentage of women. Although the underlying pathology has yet to be fully resolved, alterations in the renin-angiotensin-aldosterone axis, sympathetic nervous system/ renal and cardiac function have been implicated. In the thesis to be presented, the possible involvement of alterations in renal and myocardial adrenoceptor characteristics in the pathogenesis of steroid contraceptive-induced hypertension in rats was examined by radioligand binding techniques. In Chapter 2, a rat model of OC hypertension is described. Chronic low-dose administration of ethynyloestradiol (EE2), levonorgestrel (NG) or a combination of both steroids (EE2/NG) to female Sprague-Dawley rats was shown to significantly increase systolic blood pressure (SBP). Renal and cardiac hypertrophy developed in association with EE2-, EE2/NG- but not NG-induced hypertension. Moreover, whereas administration of NG alone attenuated body weight gain, combined EE2/NG administration increased body weight gain from the second week of treatment onwards. Based on the above observations, it is proposed that EE2 and NG induce hypertension in rats via different mechanisms. Although SBP was elevated to a similar maximum in all steroid-treated groups (+ 20 mmHg compared to controls), only with EE2 administration did SBP remain elevated for the duration of the 17 week treatment regimen. NG may therefore have a protective effect on blood pressure with long-term combined steroid contraceptive treatment. In Chapter 4, renal adrenoceptors were characterized using radioactively labelled adrenocephor antagonists. Under appropriate conditions, binding of [3H]-prazosin and [3H]-rauwolscine to membrane preparations of whole rat kidney displayed the kinetics, saturability and specificity of α1- and α2 -adrenoceptors respectively, which were present in a ratio 3:1. In contrast, [3H]-dihydroergocryptine ([3H]-DHE) apparently bound to both α1 and α2-adrenoceptors. Binding sites identified by [125I] –iodocyanopindolol (ICYP) had the recognition characteristics of β-adrenoceptors. In drug competition studies using the subtype-selective antagonists practolol (β1) and ICI 118,551 (β2)/ the ratio of β1- to β2 -adrenoceptors was found to be approximately 2:1. Subsequently, renal adrenoceptors were investigated at various stages during the development of hypertension with the different steroid contraceptive treatments (Chapters 5 and 6). Preliminary binding studies with [3H]-DHE and [3H]-prazosin suggested that the number of renal α2 - but not α1-adrenoceptors was reduced in rats with established EE2-induced hypertension (17 weeks treatment). This was subsequently confirmed using [3H]-rauwolscine, which in addition showed that the reduction in renal α2 -adrenoceptor number occurred during the developmental stage of EE2/NG~induced hypertension (6 weeks treatment) and established EE2-induced hypertension (12 weeks treatment). NG induced hypertension was unassociated with changes in renal α1- and α2-adrenoceptor characteristics. Renal β-adrenoceptor affinity was reduced in established EE2-, but not NG- or EE2/NG- induced hypertension. Moreover, the β-adrenoceptor agonist (-)-isoprenaline bound to renal β-adrenoceptors with reduced affinity following EE2 administration. Several endogenous and synthetic steroids were found to be ineffective inhibitors of [3H] –prazosin, [3H] –rauwolscine and ICYP binding excluding a direct interaction of these steroids with renal α1-, α2- and β -adrenoceptors. In Chapter 7, myocardial adrenoceptors were characterized and investigated in steroid-treated rats. In membrane preparations of whole myocardium, [3H]-prazosin binding was characteristically to α1- adrenoceptors, whereas there was a notable absence of [3H]-rauwolscine binding. Using ICYP, β-adrenoceptors were also detected, the ratio of β1- to β2~adrenoceptors being 3:1. Steroid contraceptive-induced hypertension was not associated with myocardial α1-adrenoceptor changes. Similarly, myocardial β-adrenoceptors were unchanged in established EE2-, NG- and EE2/NG-induced hypertension (12 weeks treatment). The affinity of (-)-isoprenaline for myocardial β-adrenoceptors was unaffected by EE2 aditiinistration. These studies suggest that established EE2- but not NG-induced hypertension in rats is associated with selective alterations in renal α2- and (β-adrenoceptors. These adrenoceptor changes may help to maintain elevated blood pressure by affecting the control of renal function by the sympathetic nervous system, catecholamines and several hormones which affect renin release and the transport of fluid and electrolytes in the nephron.

Two prospective investigations of periodicity of sexual behavior, well-being and testosterone (T) levels in women using and not using oral contraceptives (OCs) found no relationship between daily ratings of sexual desire and well-being across one pill and menstrual cycle. T, but not estradiol or progesterone, was positively correlated with sexual desire and sexual enjoyment in OC-users when T levels were below normal menstrual values. Other evidence suggested on association between post-ovulatory decreases in T and sexual desire in women. A bias to attend to sexual stimuli on a dichotic listening task was associated with sexual arousability in men. Moreover, task performance indicated T may enhance attention to relevant stimuli. While social variables are clearly important determinants of sexual behavior, these findings suggest a relationship between T and cognitive aspects of sexual behavior in young, healthy individuals.

Two studies are presented which investigated the relationship between oral contraceptives (o.c.s) and premenstrual changes in mood and physical state. The retrospective pilot study examined possible differences in symptom-reporting between groups of pill-users and non-users. Women using o.c.s had lower severity scores on a number of physical and mood-related symptoms compared to non-users. In the prospective study, eighty-two women with complaints of moderate to severe premenstrual symptoms were recruited for a double-blind, controlled trial of a triphasic o.c. Subjects made daily ratings of symptoms for one to two baseline cycles and were then randomly assigned to receive either placebo or the o.c. for three treatment cycles. Prospective assessment of symptoms was made using a variety of measures, and circulating levels of estrogen and progesterone were measured at three points during the cycle. Bloating and breast pain showed a greater reduction in the o.c. group than in the placebo group. In a subgroup of women with premenstrual depressive change, the o.c. also produced greater improvement in a number of symptoms compared to placebo. For all other symptoms, there was no beneficial effect of the active treatment over placebo. Women who received o.c.s reported decreased sexual interest after starting the pill. Possible hormonal mechanisms for these effects are discussed.

459 Indian female patients between the ages of 16 and 50. attending the practice of the researcher were asked to complete a confidential questionnaire on the knowledge and utilisation of contraception. The results of the study revealed that the majority of the participants were literate and possessed some knowledge of contraception. The contraceptive choice was the Pill with many participants also favouring the use of the intra uterine device. Condoms were used by only ten percent of the group while the use of the injection - Depot Provera - was negligible. Most peri menopausal women had completed their families and had undergone Tubal Ligation even though a fair number had the intra uterine device in place and also had continued using the Pill as their contraceptive. / Theses (M.Fam.Med.)-University of Natal, Durban 1995.

Graduation date: 1980

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 5 uppsatser.

Thesis (Ph.D.) - University of Glasgow, 2008. / PhD thesis submitted to the Medical Research Council, Social and Public Health Sciences Unit. Includes bibliographical references. Print version also available.

Thesis (Ph. D.)--University of Oregon, 2007. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 193-218). Also available online in ProQuest, free to University of Oregon users.