Beyond hormone replacement: quality of life in women with congenital hypogonadotropic hypogonadism

Shota Dzemaili, Jitske Tiemensma, Richard Quinton, Nelly Pitteloud, Diane Morin, Andrew A Dwyer, Shota Dzemaili, Jitske Tiemensma, Richard Quinton, Nelly Pitteloud, Diane Morin, Andrew A Dwyer

Abstract

Objective: Little is known about how women with isolated GnRH deficiency cope with their condition. This study aimed to examine the health and informational needs of women with congenital hypogonadotropic hypogonadism (CHH) and evaluate if their experiences differ from women with more common forms of infertility.

Design: Cross-sectional, multiple methods study using web-based data collection to reach dispersed rare disease patients.

Methods: A community-based participatory research framework was employed to develop an online survey and collect quantitative and qualitative data. Adult women diagnosed with CHH who had received at least one year of hormonal treatment completed the Morisky Medication Adherence Scale, Revised Illness Perception Questionnaire and Zung Self-Rating Depression Scale. Information on health care experiences, treatment outcomes and patient-reported challenges were also collected.

Results: Women (n = 55) were often diagnosed late (20.7 ± 7.4, range: 10-48 years) and 16/20 patients receiving fertility treatment conceived. Poor adherence was frequently observed (34/55) while more than half (27/49) reported a gap in treatment exceeding a year. Low adherence correlated with depressive symptoms (r = 0.3, P > 0.05). Negative illness perceptions were pervasive and 30/55 exhibited some depressive symptoms - significantly greater than women with common female factor infertility (P < 0.01). Symptoms were underappreciated by providers as only 15 of 55 patients had discussions about psychological services. Women identified isolation, need for information and finding expert care as challenges to living with CHH.

Conclusions: Despite being a treatable form of female infertility, the presumable availability of treatment does not necessarily ensure adequate quality of life for women with isolated GnRH deficiency.

Keywords: Kallmann syndrome; female infertility; illness perceptions; medication adherence; patient-centered care; rare diseases.

© 2017 The authors.

Figures

Figure 1
Figure 1
Age at CHH diagnosis and self-reported adherence to treatment. (A) Age at CHH diagnosis for 55 women ranged from 10 to 48 years. The mean age at menarche for Caucasian females is shown as a horizontal line, and the shaded region depicts ± two s.d. (36). Only 11/55 women were diagnosed by age 15 years. (B) Self-reported adherence to treatment (n = 49). Approximately one-quarter of respondents reported never having a gap in treatment. In total, more than half (27/49) reported a gap in treatment of a year or longer. Similarly 20/46 women reported having a lapse in health care exceeding one year (data not shown). Age at diagnosis was moderately correlated with duration of gap in health care (r = 0.56, P < 0.001).

References

    1. Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLOS Medicine 2012. 9 e1001356 (10.1371/journal.pmed.1001356)
    1. Balasubramanian R, Crowley WF., Jr. Isolated GnRH deficiency: a disease model serving as a unique prism into the systems biology of the GnRH neuronal network. Molecular and Cellular Endocrinology 2011. 346 4–12. (10.1016/j.mce.2011.07.012)
    1. Caronia LM, Martin C, Welt CK, Sykiotis GP, Quinton R, Thambundit A, Avbelj M, Dhruvakumar S, Plummer L, Hughes VA, et al. A genetic basis for functional hypothalamic amenorrhea. New England Journal of Medicine 2011. 364 215–225. (10.1056/NEJMoa0911064)
    1. Boehm U, Bouloux PM, Dattani MT, de Roux N, Dode C, Dunkel L, Dwyer AA, Giacobini P, Hardelin JP, Juul A, et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism-pathogenesis, diagnosis and treatment. Nature Reviews Endocrinology 2015. 11 547–564. (10.1038/nrendo.2015.112)
    1. Shaw ND, Seminara SB, Welt CK, Au MG, Plummer L, Hughes VA, Dwyer AA, Martin KA, Quinton R, Mericq V, et al. Expanding the phenotype and genotype of female GnRH deficiency. Journal of Clinical Endocrinology and Metabolism 2011. 96 E566–E576. (10.1210/jc.2010-2292)
    1. Dwyer AA, Raivio T, Pitteloud N. Management of endocrine disease: reversible hypogonadotropic hypogonadism. European Journal of Endocrinology 2016. 174 R267–R274. (10.1530/EJE-15-1033)
    1. Seminara SB, Hayes FJ, Crowley WF., Jr. Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann’s syndrome): pathophysiological and genetic considerations. Endocrine Reviews 1998. 19 521–539.
    1. Quinton R, Duke VM, Robertson A, Kirk JM, Matfin G, de Zoysa PA, Azcona C, MacColl GS, Jacobs HS, Conway GS, et al. Idiopathic gonadotrophin deficiency: genetic questions addressed through phenotypic characterization. Clinical Endocrinology 2001. 55 163–174. (10.1046/j.1365-2265.2001.01277.x)
    1. Bry-Gauillard H, Trabado S, Bouligand J, Sarfati J, Francou B, Salenave S, Chanson P, Brailly-Tabard S, Guiochon-Mantel A, Young J. Congenital hypogonadotropic hypogonadism in females: clinical spectrum, evaluation and genetics. Annales d'Endocrinologie 2010. 71 158–162. (10.1016/j.ando.2010.02.024)
    1. Martin KA, Hall JE, Adams JM, Crowley WF., Jr. Comparison of exogenous gonadotropins and pulsatile gonadotropin-releasing hormone for induction of ovulation in hypogonadotropic amenorrhea. Journal of Clinical Endocrinology and Metabolism 1993. 77 125–129.
    1. Chiaffarino F, Baldini MP, Scarduelli C, Bommarito F, Ambrosio S, D’Orsi C, Torretta R, Bonizzoni M, Ragni G. Prevalence and incidence of depressive and anxious symptoms in couples undergoing assisted reproductive treatment in an Italian infertility department. European Journal of Obstetrics & Gynecology and Reproductive Biology 2011. 158 235–241. (10.1016/j.ejogrb.2011.04.032)
    1. Garrido Oyarzun MF, Castelo-Branco C. Sexuality and quality of life in congenital hypogonadisms. Gynecological Endocrinology 2016. 32 947–950. (10.1080/09513590.2016.1241229)
    1. Wallerstein N, Duran B. Community-based participatory research contributions to intervention research: the intersection of science and practice to improve health equity. American Public Health 2010. 100 (Supplement 1) S40–S46. (10.2105/AJPH.2009.184036)
    1. Dwyer AA, Quinton R, Morin D, Pitteloud N. Identifying the unmet health needs of patients with congenital hypogonadotropic hypogonadism using a web-based needs assessment: implications for online interventions and peer-to-peer support. Orphanet Journal of Rare Diseases 2014. 9 83 (10.1186/1750-1172-9-83)
    1. Chew LD, Griffin JM, Partin MR, Noorbaloochi S, Grill JP, Snyder A, Bradley KA, Nugent SM, Baines AD, Vanryn M. Validation of screening questions for limited health literacy in a large VA outpatient population. Journal of General Internal Medicine 2008. 23 561–566. (10.1007/s11606-008-0520-5)
    1. Krousel-Wood M, Islam T, Webber LS, Re RN, Morisky DE, Muntner P. New medication adherence scale versus pharmacy fill rates in seniors with hypertension. American Journal of Managed Care 2009. 15 59–66.
    1. Morisky DE, DiMatteo MR. Improving the measurement of self-reported medication nonadherence: response to authors. Journal of Clinical Epidemiology 2011. 64 255–257. (10.1016/j.jclinepi.2010.09.002)
    1. Morisky DE, Ang A, Krousel-Wood M, Ward HJ. Predictive validity of a medication adherence measure in an outpatient setting. Journal of Clinical Hypertension 2008. 10 348–354. (10.1111/j.1751-7176.2008.07572.x)
    1. Zung WW. A self-rating depression scale. Archives of General Psychiatry 1965. 12 63–70. (10.1001/archpsyc.1965.01720310065008)
    1. Zung WW. The role of rating scales in the identification and management of the depressed patient in the primary care setting. Journal of Clinical Psychiatry 1990. 51 (Supplement) 72–76.
    1. Moss-Morris R, Weinman J, Petrie K, Horne R, Cameron L, Buick D. The revised illness perception quesionnaire (IPQ-R). Psychology and Health 2002. 17 1–16. (10.1080/08870440290001494)
    1. Dwyer AA, Tiemensma J, Quinton R, Pitteloud N, Morin D. Adherence to treatment in men with hypogonadotrophic hypogonadism. Clinical Endocrinology 2017. 86 377–383. (10.1111/cen.13236)
    1. Barrett J, Hurst MW, DiScala C, Rose RM. Prevalence of depression over a 12-month period in a nonpatient population. Archives of General Psychiatry 1978. 35 741–744. (10.1001/archpsyc.1978.01770300083009)
    1. Tiemensma J, Kaptein AA, Pereira AM, Smit JW, Romijn JA, Biermasz NR. Affected illness perceptions and the association with impaired quality of life in patients with long-term remission of acromegaly. Journal of Clinical Endocrinology and Metabolism 2011. 96 3550–3558. (10.1210/jc.2011-1645)
    1. Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GG, Hasemeier CM. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics 1997. 99 505–512. (10.1542/peds.99.4.505)
    1. Saldana J. Coding Manual for Qualitative Researchers. Thousand Oaks, CA, USA: Sage, 2009.
    1. Filicori M, Flamigni C, Dellai P, Cognigni G, Michelacci L, Arnone R, Sambataro M, Falbo A. Treatment of anovulation with pulsatile gonadotropin-releasing hormone: prognostic factors and clinical results in 600 cycles. Journal of Clinical Endocrinology and Metabolism 1994. 79 1215–1220.
    1. Gronier H, Peigne M, Catteau-Jonard S, Dewailly D, Robin G. Ovulation induction by pulsatile GnRH therapy in 2014: literature review and synthesis of current practice. Gynécologie Obstétrique & Fertilité 2014. 42 732–740. (10.1016/j.gyobfe.2014.07.017)
    1. Rastrelli G, Corona G, Mannucci E, Maggi M. Factors affecting spermatogenesis upon gonadotropin-replacement therapy: a meta-analytic study. Andrology 2014. 2 794–808. (10.1111/andr.262)
    1. Hofmann J, Watzlawik M, Richter-Appelt H. Living with Kallmann syndrome – analysis of subjective experience reports from women. Geburtshilfe Frauenheilkd 2013. 73 1112–1120. (10.1055/s-0033-1350881)
    1. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Archives of Internal Medicine 2000. 160 2101–2107. (10.1001/archinte.160.14.2101)
    1. Dwyer AA, Quinton R, Pitteloud N, Morin D. Psychosexual development in men with congenital hypogonadotropic hypogonadism on long-term treatment: a mixed methods study. Sexual Medicine 2015. 3 32–41. (10.1002/sm2.50)
    1. Quinton R. Phenotypic Aspects of Kallmann Syndrome. Cambridge, UK: University of Cambridge, 2001.
    1. Carel JC, Elie C, Ecosse E, Tauber M, Leger J, Cabrol S, Nicolino M, Brauner R, Chaussain JL, Coste J. Self-esteem and social adjustment in young women with Turner syndrome – influence of pubertal management and sexuality: population-based cohort study. Journal of Clinical Endocrinology and Metabolism 2006. 91 2972–2979. (10.1210/jc.2005-2652)
    1. Ros C, Alobid I, Balasch J, Mullol J, Castelo-Branco C. Turner’s syndrome and other forms of congenital hypogonadism impair quality of life and sexual function. American Journal of Obstetrics and Gynecology 2013. 208 e481–e486. (10.1016/j.ajog.2012.10.876)
    1. Pletcher BA, Toriello HV, Noblin SJ, Seaver LH, Driscoll DA, Bennett RL, Gross SJ. Indications for genetic referral: a guide for healthcare providers. Genetics in Medicine 2007. 9 385–389. (10.1097/GIM.0b013e318064e70c)
    1. Harper J, Geraedts J, Borry P, Cornel MC, Dondorp WJ, Gianaroli L, Harton G, Milachich T, Kaariainen H, Liebaers I, et al. Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. Human Reproduction 2014. 29 1603–1609. (10.1093/humrep/deu130)
    1. Au MG, Crowley WF, Jr, Buck CL. Genetic counseling for isolated GnRH deficiency. Molecular and Cellular Endocrinology 2011. 346 102–109. (10.1016/j.mce.2011.05.041)
    1. Laitinen EM, Hero M, Vaaralahti K, Tommiska J, Raivio T. Bone mineral density, body composition and bone turnover in patients with congenital hypogonadotropic hypogonadism. International Journal of Andrology 2012. 35 534–540. (10.1111/j.1365-2605.2011.01237.x)
    1. Divasta AD, Gordon CM. Hormone replacement therapy and the adolescent. Current Opinion in Obstetrics and Gynecology 2010. 22 363–368. (10.1097/GCO.0b013e32833e4a35)
    1. Dwyer AA, Phan-Hug F, Hauschild M, Elowe-Gruau E, Pitteloud N. Transition in endocrinology: hypogonadism in adolescence. European Journal of Endocrinology 2015. 173 R15–R24. (10.1530/EJE-14-0947)
    1. Godbout A, Tejedor I, Malivoir S, Polak M, Touraine P. Transition from pediatric to adult healthcare: assessment of specific needs of patients with chronic endocrine conditions. Hormone Research in Paediatrics 2012. 78 247–255. (10.1159/000343818)
    1. Fox S. Peer-to-peer healthcare: many people – especially those living with chronic or rare diseases – use online connections to supplement professional medical advice. In Pew Internet and Americal Life Project, p 26 Washington DC, USA: Pew Research Center, 2011.
    1. Committee on Quality Health Care in America, Institute of Medicine. Crossing The Quality Chasm: a New Health System for the 21st Century. Washington DC, USA: National Academy Press, 2001.
    1. Frampton S, Guastello S, Brady C, Hale M, Horowitz S, Bennett-Smith S, Stone S. Picker Institute Patient-centered Care Improvement Guide. Derby, UK: CT Planetree, Inc., 2008.

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