Case Report: Hypothalamic Amenorrhea Following COVID-19 Infection and Review of Literatures

Paolo Facondo; Virginia Maltese; Andrea Delbarba; Ilenia Pirola; Mario Rotondi; Alberto Ferlin; Carlo Cappelli

doi:10.3389/fendo.2022.840749

Reproductive Endocrinology Neuroendocrinology

Case Report: Hypothalamic Amenorrhea Following COVID-19 Infection and Review of Literatures

Facondo P, Maltese V, Delbarba A, Pirola I, Rotondi M, Ferlin A, Cappelli C

Published June 10, 2022 Frontiers in endocrinology

DOI 10.3389/fendo.2022.840749 PMID 35757408 PMC PMC9229338

RRM Academy Synopsis

Hypothalamic amenorrhea followed COVID-19 in a 36-year-old woman

A healthy 36-year-old woman developed hypothalamic amenorrhea after COVID-19 infection, according to a case report from Italy. The woman, who had regular cycles before the illness, had no return of her cycle at the last assessment. Hormone stimulation tests suggested hypothalamic impairment. The authors hypothesize that the infection may have caused it.

Key Findings

The woman, 36, had regular cycles until March 8, 2021, her last menstruation. A positive swab came on March 15, 2021, and her symptoms cleared in 12 days without treatment.
At her September 2021 evaluation she reported secondary amenorrhea for 6 months. The workup excluded pregnancy, polyendocrine metabolic ovarian syndrome (PMOS / PCOS), other gynecologic causes, overt primary thyroid disease and hyperprolactinemia.
Brain MRI showed an uncertain millimetric pituitary microadenoma and no hypothalamic abnormality. Blood tests showed hypogonadotropic hypogonadism, and gonadotropins rose after a GnRH analogue test, suggesting hypothalamic deficiency.
Ten days after the GnRH analogue test she had menstrual spotting for a few days. On November 3, 2021, hypogonadotropic hypogonadism persisted without resumption of the menstrual cycle.
The authors' review lists pituitary apoplexy and SIADH as the most reported hypothalamic-pituitary alterations after COVID-19 and, to their knowledge, finds no earlier report of female hypogonadotropic hypogonadism with secondary amenorrhea.

Interpretation

This case report describes one patient in detail and presents a hypothesis for the mechanism. The authors support the hypothesis with the timing and with ACE2 receptors: the virus uses these receptors to enter cells, and the receptors have been observed in the hypothalamus. The patient reported no psychosocial stress, excessive exercise or significant weight change. The authors note that direct evidence of the virus in hypothalamic tissue is still missing and call for more cases. The findings support further study of COVID-19 as a trigger for hypothalamic amenorrhea.

RRM Context

Restorative reproductive medicine treats a missing cycle as a finding with a cause. The authors made this diagnosis by ruling out other causes first, as current guidelines advise for secondary amenorrhea. Cycle charting gives a day-by-day record of when a cycle changes.

Our editorial summary of this paper, not the article's abstract.

Abstract

SARS-CoV-2 infection, responsible for the coronavirus disease 2019 (COVID-19), can impair any organ system including endocrine glands. However, hypothalamic-pituitary dysfunctions following SARS-CoV-2 infection remain largely unexplored. We described a case of hypothalamic amenorrhea following SARS-CoV-2 infection in a 36-year-old healthy woman. The diagnostic workup excluded all the causes of secondary amenorrhea, in agreement to the current guidelines, whereas the gonadotropin increase in response to GnRH analogue tests was suggestive for hypothalamic impairment. Therefore, since our patient did not present any organic cause of hypothalamic-pituitary disorder, we hypothesized that her hypothalamic deficiency may have been a consequence of SARS-CoV-2 infection. This assumption, besides on the temporal consecutio, is strengthened by the fact that SARS-CoV-2 infection can impair the hypothalamic circuits, altering the endocrine axes, given that angiotensin-converting enzyme 2 receptors have also been observed in the hypothalamus. We reviewed the literature regarding hypothalamic-pituitary dysfunction in patients with SARS-CoV-2 infection. No study has previously described female hypogonadotropic hypogonadism with secondary amenorrhea following COVID-19. We suggest clinicians focusing greater attention on this possible endocrine disorder.

Topics

Reproductive Endocrinology › Neuroendocrinology › Hypothalamic Amenorrhea · Menstrual Cycle › Cycle Disorders › Amenorrhea

Paolo Facondo, Virginia Maltese, Andrea Delbarba, Ilenia Pirola, Mario Rotondi, Alberto Ferlin, Carlo Cappelli

P Facondo, V Maltese, A Delbarba, I Pirola, M Rotondi, A Ferlin, C Cappelli

PMID 35757408 35757408 DOI 10.3389/fendo.2022.840749 10.3389/fendo.2022.840749 Facondo et al. 2022, Facondo 2022

Case Report: Hypothalamic Amenorrhea Following COVID-19 Infection and Review of Literatures

Hypothalamic amenorrhea followed COVID-19 in a 36-year-old woman

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

Related research