Hormone Replacement Therapy For Symptoms Research Articles

PRIMARY OVARIAN INSUFFICIENCY, A CHALLENGING DIAGNOSIS. A CASE SERIES

INTRODUCTION
 Primary ovarian insufficiency is rare, affecting 1-2% of those under 40 with only 0.1% of cases below 30 years. Etiology is mainly idiopathic, however chromosomal defects, autoimmune processes, and iatrogenic causes are associated. Symptoms are those of menopause but of intermittent durations and severities; and management targets the symptoms and complication prevention.
 CASE PRESENTATION
 We present two 18-year-old patients of African and Indian descent with an eight and five-month history of amenorrhea respectively with otherwise unremarkable history and physical exams. Investigation showed elevated FSH levels of 45.07 and 88.73 mIU/ml done four weeks apart in the first patient and 68.69 in the second patient. All other parameters were normal.
 DISCUSSION
 Aetiology is mainly idiopathic. 10-12% of diagnosed patients have chromosomal abnormalities such as Turner’s syndrome, fragile X syndrome, and genetic permutations of FMR 1 gene. Autoimmune causes are mainly autoimmune adrenal diseases. Autoimmune thyroiditis, Dermatomyosistis and Diabetes Mellitus type 1 also show association. Mumps Oophritis is the main infectious cause. Laparoscopic surgical procedures that involve the ovaries or affect their blood supply, pelvic radiotherapy, and chemotherapy all comprise the iatrogenic causes. Lifestyle and environmental factors such as smoking and heavy metals exposure also contribute.
 Diagnosis is by serum FSH levels of above 25 IU/l in two separate readings four weeks apart with a four-month history of amenorrhea occurring before 40 Years. Both patients were under 30 and met the criteria.
 Management involves hormone replacement therapy for symptoms, prevention and treatment of osteoporosis, oocyte donation for infertility, and counseling for both the psychological impact of the disease and the numerous complications living with the disease.
 CONCLUSION
 Multidisciplinary care is necessary for management of this rare and challenging illness

Interaction between estradiol and tacrolimus in kidney-transplanted menopausal women

Sir, Hormone replacement therapy for symptoms caused by oestrogen deficiency is often used by menopausal women. Transdermal administration is regularly used by means of a dermal application gel. Its active principle, the synthesis 17β estradiol, is a well-known substance known as an inhibitor of the microsomial cytochrome P450 enzymatic system. We present the case of a kidney transplant woman who faced a brutal degradation of her graft function consequent to an increase of her tacrolimus plasma level. This 65-year-old patient had benefited from a kidney transplant as a consequence of renal insufficiency due to hyperuricaemia-induced interstitial nephropathy (uromoduline gene mutation). Her medical history also included hypertension, hysterectomy for fibroma and partial thyroidectomy. Her treatment included tacrolimus 9 mg/day, mycophenolic acid 540 mg/day, prednisolone 4 mg/day, lisinopril 20 mg/day, atorvastatin 10 mg/day, l-thyroxine 100 mg/day and alprazolam 0.5 mg/day. She had a normal post-transplant evolution with good renal function (creatinine 1.1 mg/dl, GFR estimated according to MDRD 53 ml/min/1.73 m2, plasma tacrolimus trough levels ranging between 5.0 and 7.5 ng/ml). Her renal function suddenly deteriorated 10 days after a gynaecological consultation, with a very high tacrolimus plasma level: creatinine increased to 1.6 and 2 mg/dl, GFR decreased to 28 ml/min/m2 and tacrolimus plasma trough levels reached 14.2 and 18.3 ng/ml. No other cause of graft-function loss was detected: an echography with Doppler was normal; no urinary infection was found. A thorough investigation of her medication revealed a new oestrogen gel-based treatment (Estreva 0.1%, Merck, France) requesting daily application of 0.5 mg/day (one-third of the recommended doses). Despite the small estradiol doses, plasma tacrolimus concentrations apparently significantly increased because of medical interaction between tacrolimus and the oestrogen preparation. A drastic reduction (60%) in the daily doses of tacrolimus was necessary to reach the therapeutical plasma concentrations again: the tacrolimus plasma trough level reached 6.4 ng/ml, serum creatinine 1.3 mg/dl and eGFR 44 ml/min/m2, 2 weeks after a progressive reduction in the tacrolimus dosage. Both tacrolimus and estradiol are metabolized through the CYP450 3A4 enzyme complex [1,2,5]. Tacrolimus is a well-known strong inhibitor of the 2-estradiol metabolization phases (hydroxylation and glucuronidation) [2,4], delaying its elimination. While estradiol inhibits hepatic as well as intestinal CYP450 3A4 [3], it induces a lowering in the tacrolimus metabolism. This inhibition shows an inter-individual variability [3]. The transdermic administration avoids the hepatic ‘1st passage’ phenomenon, which explains the fact that even small doses are sufficient to create a systemic effect. Co-administration of tacrolimus with oestrogen is possible, but a close monitoring of tacrolimus trough levels and renal function is necessary. Even small doses of estradiol can create severe interactions with tacrolimus; therefore, clinicians should be aware of this harmful drug interaction in order to avoid potential renal graft dysfunction. Conflict of interest statement. None declared.