Background: The association of Human Immune deficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) and sex hormone changes may grossly affect the reproductive health in affected women. This was a prospective study done at Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, Nigeria to evaluate the sex hormone changes in HIV infected women of reproductive age group during menstrual cycle. Materials and methods: A total of 90 women (60 HIV positive, 30 Control) were studied. After detailed medical examination, a well-structured questionnaire was self-administered. Blood samples were collected under sterile conditions during the follicular and luteal phases of menstrual cycle after due informed consent had been sought and obtained. The samples were analyzed for sex hormones (Progesterone, estradiol and testosterone) using Enzyme Linked Immunosorbent Assay (ELISA) method. Results: The result showed that the sex hormones (Progesterone, estradiol and testosterone) were significantly lower at both phases of the menstrual cycle in HIV infected women when compared to the Control (P&lt;0.05). Conclusion: The study revealed some degree of hypogonadism in HIV infected women which may have some implication in their reproductive life

Aboh, Nancy .A.

Ahaneku, Joseph .E.

Emelumadu, Obiagel .F.

Nnadozie, Okwudili J

Onyenekwe, Charles.C.

Ukibe, Nkiruka .R.

Ukibe, Solomon .N.

English

European Scientific Journal, ESJ

European Scientific Journal June 2015 edition vol.11, No.18  ISSN: 1857 – 7881 (Print)  e - ISSN 1857- 7431 134 SEX HORMONES CHANGES ASSOCIATED WITH MENSTRUAL CYCLE IN HIV              INFECTED FEMALES AT NAUTH, NNEWI, SOUTHEAST NIGERIA.    Nkiruka .R. Ukibe, PhD Department of Human Biochemistry, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nnewi, Anambra State, Nigeria Obiagel .F. Emelumadu, MBBS, FWACP Department of Community Medicine, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nnewi, Anambra State, Nigeria Solomon .N. Ukibe, MBBS, PhD Department of Prosthesis and Orthotics, School of Health Technology, Federal University of Technology Owerri, Nigeria Charles.C. Onyenekwe, PhD, FMLSCN Deparment of Medical Laboratory Science, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nnewi, Anambra State, Nigeria Joseph .E. Ahaneku, PhD, FSTA(jp), FSeh Department of Chemical pathology, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nnewi, Anambra State, Nigeria Nancy .A. Aboh Department of Human Biochemistry, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nnewi, Anambra State, Nigeria Okwudili J Nnadozie Department of Chemical pathology, College of Health Sciences, Nnamdi Azikiwe University, Nnewi, Campus, Nnewi, Anambra State, Nigeria   Abstract  Background: The association of Human Immune deficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) and sex hormone changes may grossly affect the reproductive health in affected women. This was a prospective study done at Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, Nigeria to evaluate the sex hormone changes in HIV infected women of reproductive age group during menstrual cycle. Materials and methods: A total of 90 women (60 HIV European Scientific Journal June 2015 edition vol.11, No.18  ISSN: 1857 – 7881 (Print)  e - ISSN 1857- 7431  135 positive, 30 Control) were studied. After detailed medical examination, a well-structured questionnaire was self-administered.  Blood samples were collected under sterile conditions during the follicular and luteal phases of menstrual cycle after due informed consent had been sought and obtained. The samples were analyzed for sex hormones (Progesterone, estradiol and testosterone) using Enzyme Linked Immunosorbent Assay (ELISA) method. Results: The result showed that the sex hormones (Progesterone, estradiol and testosterone) were significantly lower at both phases of the menstrual cycle in HIV infected women when compared to the Control (P<0.05). Conclusion: The study revealed some degree of hypogonadism in HIV infected women which may have some implication in their reproductive life.   Keywords: Sex hormones, HIV Women, Menstrual Cycle, Southeast Nigeria   Introduction  The Human Immune deficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) is a leading cause of morbidity and mortality among women of reproductive age in Nigeria (UNAIDS 2011; NACA 2012). 1.72 million (58%) out of 3.1 million people living with HIV/AIDS in Nigeria are females within their reproductive age (15-45 years) (UNAIDS 2011; UNAIDS 2012). This shows increased burden of HIV on the female population when compared to their male counterparts.   HIV has been known to impact negatively on women’s reproductive health (Ikechebelu et al., 2002; Fallahian and Ilkhani, 2006). The negative reproductive impact ranges from menstrual disorders to outright infertility. Some of these disorders may be as a result of deranged ovarian function with far reaching effects on sex hormones.  The present study was therefore designed to evaluate sex hormones changes associated with menstrual cycle in HIV infected premenopausal female subjects in Nnewi, Anambra State, Nigeria.   Materials and methods  The sample population consisted of ninety premenopausal female participants within the age range (15-45years). Thirty participants were apparently healthy controls recruited amongst the Hospital staff. Thirty participants were HIV seropositive females who have not been placed on antiretroviral therapy while the remaining thirty were HIV seropositive female participants who have been placed on antiretroviral therapy for not less than six months. They were recruited at the HIV clinic of Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State Nigeria. European Scientific Journal June 2015 edition vol.11, No.18  ISSN: 1857 – 7881 (Print)  e - ISSN 1857- 7431 136  After obtaining informed consent of the participants, a well detailed questionnaire was administered to each participant to ascertain their medical and reproductive history. 8 millimeters of venous blood was collected aseptically between 9.00am and 12noon from each participant at follicular (7-13th day) and luteal (21-23rd day) phases of menstrual cycle. All the participants were double screened for malaria parasite and HIV infection using rapid antigen diagnostic techniques for malaria falciparum and immunoassay and immunochromatographic methods for HIV screening respectively. The serum content was separated immediately after clot retraction, labeled and stored at -20oC for determination of estradiol, progesterone and testosterone using ELISA (Enzyme Linked Immunosorbent Assay) method.   The ethics committee of NAUTH Nnewi approved the study design and only those who gave their consent were recruited for the study.   Inclusion and Exclusion criteria: only the participant adjudged as HIV stage 2 were recruited for the study. HIV stage 1, stage 3 and stage 4 were excluded, participant with malaria parasite infection as at the time of study were excluded, participants on contraceptives were excluded, women with previous history of infertility prior to the study and participants who were co-infected with tuberculosis were also excluded from the study. Hence the female participants used were those with no prior fertility problems until the existence of HIV infection.  Methods  Antibodies to HIV-1 and HIV-2 in Human Plasma were detected using Abbott Deterimine system, Immunoassay method [(Trinity Biotech UniGold Assay Kit (Trinity Biotech PLC, Ireland)] and imunochromatographic method [(HIV 1 and 2 STAT-PAK Assay kit (Chembio diagnostic system, INC New York, USA)] respectively.  Determination of Progesterone, Estradiol and testosterone were done using Enzyme Linked Immunosorbent Assay (ELISA) kits (Glory Science Laboratory USA)  Statistical analysis  The version 16 of SPSS package was used in statistical analysis. The variables were expressed as mean (±SD). The student t-test and analysis of variance (ANOVA) and post-hoc (LSD) were used to assess significant mean differences. Graph Pad Prism version 5.03 was used for graph presentations.  European Scientific Journal June 2015 edition vol.11, No.18  ISSN: 1857 – 7881 (Print)  e - ISSN 1857- 7431  137 Results Levels of Sex Hormone (Progesterone) at follicular and luteal phases of menstrual cycle  The mean (±SD) serum Progesterone concentration (ng/ml) in HIV seropositive females and HIV seropositive females on ART was not significantly different between follicular (1.9±0.7, 2.5±2.0) and luteal (1.9±0.3, 2.1±1.8) phases of menstrual cycle (P>0.05 respectively). But the mean serum progesterone concentration (ng/ml) dropped significantly at follicular phase (4.4±2.5) compared with the luteal phase (8.7±4.9) of menstrual cycle in Control female subjects (P<0.05).   When the mean progesterone concentration (ng/ml) at follicular and luteal phases of menstrual cycle were compared between the Control group and the Test groups, the mean progesterone concentration dropped significantly in HIV seropositive (1.9±0.7, 1.9±0.3) and HIV seropositive on ART (2.5±2.0, 2.1±1.8) compared with follicular and luteal values in the Control female subjects (4.4±2.5, 8.7±4.9) (P<0.05 respectively) (See Fig 1).  Levels of Sex Hormone (Estradiol) at follicular and luteal phases of menstrual cycle  The mean (±SD) serum estradiol Concentration (pg/ml) in HIV seropositive females and HIV seropositive females on ART was not significantly different between follicular (24.2±18.7, 32.8±20.2) and luteal (18.7±11.2, 38.4±24.0) phases of menstrual cycle (P>0.05 respectively). Conversely, the mean estradiol value (pg/ml) dropped significantly at follicular phase (80.9±36.6) compared with luteal phase (94.1±50.1) of menstrual cycle in Control female subjects (P<0.05).  When the mean estradiol concentration (ng/ml) at follicular and luteal phases of menstrual cycle were compared between the Control group and Test groups, the mean estradiol dropped significantly in   HIV seropositive females (24.2±18.3, 18.7±11.2) and HIV seropositive females on ART (32.8±20.2, 38.4±24.0) compared with follicular and luteal values in the Control female subjects (80.9±36.6, 94.1±50.1) (P<0.05 respectively) (see fig 2).  Levels of Sex Hormone (Testosterone) at follicular and luteal phases of menstrual cycle  The mean (±SD) serum testosterone level (ng/ml) in HIV seropositive females was not significantly different between follicular (0.30±0.17) and luteal (0.30±0.15) phases of the cycle (P>0.05). In HIV seropositive females on ART, there was no significant difference in the mean testosterone concentration (ng/ml) between the follicular (0.41±0.27) and luteal (0.36±0.15) phases of menstrual cycle (P>0.05). But the mean serum European Scientific Journal June 2015 edition vol.11, No.18  ISSN: 1857 – 7881 (Print)  e - ISSN 1857- 7431 138 testosterone value (ng/ml) dropped significantly at luteal (0.81±0.27) phase of menstrual cycle compared with follicular phase (1.08±0.48) in the Control female subjects (P<0.05).  When the Mean Testosterone concentration (ng/ml) at follicular and luteal phase of menstrual cycle were compared between the Control group and Test groups, the Mean Testosterone level dropped significantly in HIV seropositive females (0.30±0.17, 0.30±0.15) and HIV seropositive females on ART (0.41±0.27, 0.36±0.15) compared with the corresponding values in the Control female subjects (1.08±0.48, 0.81±0.27) (P<0.05 respectively).   The pos hoc analysis showed significantly higher mean testosterone concentration (pg/ml) at follicular and luteal phases of menstrual cycle in HIV seropositive females on ART (0.41±0.27, 0.36±0.15) compared with the corresponding values in HIV seropositive female subjects (0.30±0.17, 0.30±0.15 respectively) (See Fig 3).   European Scientific Journal June 2015 edition vol.11, No.18  ISSN: 1857 – 7881 (Print)  e - ISSN 1857- 7431  139   European Scientific Journal June 2015 edition vol.11, No.18  ISSN: 1857 – 7881 (Print)  e - ISSN 1857- 7431 140 Discussion   The present study showed that the mean serum levels of progesterone and estradiol in HIV seropositive females was not significantly different between follicular and luteal phases of menstrual cycle. This contrasts the observation in apparently healthy subjects where differences in hormonal levels exist between the two phases of the menstrual cycle. FSH and LH are usually higher at the follicular phase and peak at the mid cycle to enable ovulation take place (Norman, 2001) while Progesterone and estradiol are usually higher at the luteal phase. The absence of this normal physiological balance in the test subjects may cause changes in the cycle which may affect reproductive function. Significant reductions in the level of progesterone at the luteal phase may disturb the sustenance of pregnancy and lead to spontaneous abortion while gross reductions in these hormones (hypogonadism) may cause failure of menstruation or significant abnormality in menstrual cycle. All these factors may play significant role in the pathogenesis of infertility in affected women.   The serum levels of progesterone and estradiol levels were significantly lower in HIV seropositive and HIV seropositive females on ART at both follicular and luteal phases of menstrual cycle. The implication of grossly reduced progesterone is primary ovarian failure. This means that the anterior pituitary may be overworking itself to stimulate a poorly responding ovary. The abnormally low progesterone signifies hypogonadism and may lead to menstrual and reproductive failure. Some previous studies done developed countries (Merrill et al., 1989; Tracy and Cerami, 1990) produced a similar report. Hypogonadism is a significant cause of infertility in HIV women (Grinspoon et al., 1997).   The appreciation in the level of progesterone in HIV seropositive subjects on ART suggests stimulatory effects of the treatment on the gonads with intact negative feedback mechanism thereby resulting in the restoration of the gonadal functions showing some beneficial effects and a tendency to return to normal. This may reduce the incidence of menstrual abnormality and infertility. Unfortunately however, studies have reported that prolonged use of ART especially protease inhibitors have been associated with other problems such as hyper prolactinaemia (Hutchinson et al., 2000).  Hyper prolactinaemia has been associated with increased incidence of anovulation and hence infertility (Ikechebelu et al., 2002).   Studies of ovarian function in HIV infected women have produced controversial reports. Whereas some authors (Chargwin et al., 1996; Harlow et al., 2000) reported significant effects of HIV on ovarian function, others (Shah et al., 1994; Ellerbrock et al., 1996) reported no significant change in ovarian function. This controversy is believed to be due to the fact that most of the studies were done in advanced or industrialized countries where European Scientific Journal June 2015 edition vol.11, No.18  ISSN: 1857 – 7881 (Print)  e - ISSN 1857- 7431  141 women who were advanced in age were the participants and the studies did not consider the phases of their menstrual cycle. Such women were said to have poor ovarian reserve since most of them were premenopausal (Panda et al., 2013). In the present study however, the participants were women within their reproductive age (15-45years) at different phases of their menstrual cycle and the effects of HIV on the ovarian function will be more pronounced.              The significantly lower level of testosterone observed in HIV seropositive and  HIV seropositive female subjects on ART when compared to Control females is also due to the reduced ovarian function. In normal physiology, testosterone is produced by the ovaries in the females in very small quantities which serve to maintain muscle mass and hence prevents weight loss. In diseased individuals, this quantity becomes much smaller because of reduced ovarian function and is not able to achieve its physiological function anymore hence the excess weight loss that is associated with these diseases (HIV inclusive) (Huang et al., 2003).                In Conclusion, the study showed significant reduction in the sex steroid hormones indicating reduced ovarian function (hypogonadism) which accounts for menstrual changes that can lead to infertility in the affected women.   References: Chirgwin KD, Feldman F, Muneyyirci-Delale O. Menstrual function in Immunodeficiency Virus-infected women without Acquired Immunodeficiency Syndrome. Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology 1996; 12(4): 489-494. Ellerbrock TV, Wrght TC, Bush TJ, Dole P, Brudney K, Chiasson MA. Characteristics of menstruation in women infected with Human Immunodeficiency Virus. Obstetrics and Gynecology 1996; 87(6): 1030-1034. Fallahian M, IIkhani M. Menstrual Disorders in Nongenital Tuberculosis.  Infectious Disease in Obstetrics and Gynaecology 2006; 18452:1–3. Grinspoon S, Corcoran C, Kareem M, Biller BMK, ASkari H, Wang E, Hubbard J, Anderson EJ, Basgoz N, Heller HM, and Klibansky A. Body Composition and Endocrine function in Women with Acquired Immunodeficiency Syndrome Wasting. Journal of Clinical Endocrinology and Metabolism 1997; 82(5):1332-1336. Harlow SD Schuman P, Cohen M, Ohmit SE Cu-Uvin S, Lin X, Anastos K, Burns D, green blath R, Minkoff A, Muderspach L, Rompalo A, Warren D, Young MA Klein RS. Effect of HIV infection on menstrual cycle length. Journal of Acquired immune Deficiency Syndrome 2000; 24(1):68-75 European Scientific Journal June 2015 edition vol.11, No.18  ISSN: 1857 – 7881 (Print)  e - ISSN 1857- 7431 142 Hutchinson J, Murphy M, Harries R, Skinner CJ. Galactorrhoea and hyper prolactinaemia associated with protease inhibitors. Lancet 2000; 356: 1003-1004. Ikechebelu JI, Ikegwuonu SC, Joe-Ikechebelu NN. HIV Infection and Sexual behaviours among infertile women in Southwestern, Nigeria. Journal of Obstetrics and Gynecology 2002; 22(3): 306-307. Merrill JE, Koyanagi Y, Chen ISY. Interleukin -1 and tumor necrosis factor α can be induced from mononuclear phagocytes by human immunodeficiency virus type1 binding to the CD4 receptor. Journal of Virology 1989; 63(1):4404-4408 National Agency for the Control of AIDS (NACA). Federal Republic of Nigeria, Global AIDS Response Country Progress Report Nigeria.Country Progress Report 2012. Norman J. Jeffcoate’s Principles of Gynecology. 5th ed. Ansari Nagar, New DELHI, India 2001; 60-119. Panda S, Singh AS, Jha Vandana. The concepts and Consequences of Early Ovarian Ageing: A Caveat to Women’s Health. Journal of Reproduction and Infertility 2013; 14(1):3-7 Shah PN, Smith JR, Wells C, Barton SE, Kitchen VS, Steer PT. Menstrual Symptoms in women infected by the Human Immunodeficiency virus. Obstetrics Gynecology 1994; 83(4): 397-400 Tracey KJ, Cerami A. Metabolic responses to cachectin/TNF: A Brief review. Annals of Academic of Science 1990; 587 (3):325-331 UNAIDS 'World AIDS Day Report’ Nov 2011 UNAIDS ‘Global Report: Annexes' 2012 UNAIDS 'Women Out Loud: How Women Living with HIV Will Help the World End AIDS' 2012     

SEX HORMONES CHANGES ASSOCIATED WITH MENSTRUAL CYCLE IN HIV  INFECTED FEMALES AT NAUTH, NNEWI, SOUTHEAST NIGERIA

https://eujournal.org/index.php/esj/article/download/5827/5679

SEX HORMONES CHANGES ASSOCIATED WITH MENSTRUAL CYCLE IN HIV INFECTED FEMALES AT NAUTH, NNEWI, SOUTHEAST NIGERIA

Abstract

Similar works

Full text

Available Versions

European Scientific Journal, ESJ