Effect of Levothyroxine Replacement on Testosterone, Lh, Fsh Levels in Men with Over Hypothyroidism

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Nelson Vergel

Founder, ExcelMale.com
Aim- to study the effect of hypothyroidism on testicular function, and the effect of post levothyroxine replacement on testicular function.

Methods and materials- this study was done in r&r hormone clinic in central part of india, the study was interventional. 21 naïve overtly hypothyroid male patient were taken in this study. The hormones essayed were free testosterone, lh, fsh, t3, t4, tsh before and after 4 months of levothyroxine replacement therapy. Additional adams questionnaire was included in this study to evaluate the prevalance of sexual disturbance in these patients. Proper consent was taken from the patients.

Inclusion criteria- newly diagnosed hypothyroid male 20—50 years

Exclusion criteria- History of diabetes mellitus; History of hypertension; History of testicular trauma; History of hormonal replacement therapy; History of smoking, chronic alcoholism

Result- 50% of patients (10/21) at baseline had low free testosterone level value, mean value of 10-12% had low lh level value(3/21 patients), 88-90% has normal lh value(18/21 patients), fsh values of all the patients was normal, 60 % of patients has low adams score(12/21 patients).

After 4 months of therapy on restoration of euthyroidism 8 out of 10 (90%) hypogonadotropic patients the free testosterone level came normal (>300mg/dl), lh value of all the patients restored to normal values, 80% of the patients with low adams score showed improvement in their parameters.

Conclusion- there is a high prevalance of hypogonadism in hypothyroid male patients which seemed to be improved significantly after levothyroxine therapy.

Introduction

The prevalence of overt hypothyroidism ranges from 5% to 11%. Though Hypothyroidism is less common in males but thyroid hormone deficiency affects all organs of the body, including changes that alter growth hormone, glucocorticoids, and gonadal function. Primary hypothyroidism is associated with hypogonadotropic hypogonadism, which is reversible with thyroid hormone (levothyroxine) replacement therapy. Men with primary hypothyroidism have subnormal responses to (LH) or (GnRH) replacement versus significant response to (hCG). Free testosterone concentrations are decreased in men with primary hypothyroidism and thyroid hormone substitution normalizes free testosterone concentrations.

Discussion
Hypothyroidism, a common endocrine problem is known to cause significant disturbances in male reproductive function. The effect of hypothyroidism and its treatment on individual parameters like gonadotropins, prolactin, testosterone, INHB, and has not been well studied till now. In our study 50% of patients had low testosterone level at baseline, low testosterone level associated with hypothyroidism has been well documented in several studies with varying prevalences. The possible mechanisms by which hypothyroidism causes low total testosterone include reduced uptake of cholesterol into the steroidogenic cells for testosterone synthesis, inhibition of the enzymes converting progesterone to testosterone, decrease in serum sex hormone binding globulin level, hyperprolactinemia, increased rate of conversion of testosterone to estradiol, and decrease in the secretion of gonadotropins. Although pituitary imaging prolactin levels also have some role in hypogonadism associated with hypothyroidism but due to financial concerns these parameters were not taken in the study material.

In our study only 3 patients had low LH level at baseline while FSH level of all the patients was normal at baseline, semen analysis could not be done due to non consent of patients.

In our study after attainment of euthyroidism or after 4 months of replacement of levothyroxine therapy 80% of hypogonadic patients had their testosterone level normal, more than 80% of patients with low ADAMS score showed improvement in their parameters.

Conclusion
Thyroid hormone deficiency affects all tissues of the body, including multiple endocrine changes that alter growth hormone, corticotrophin, glucocorticoids, and gonadal function. Primary hypothyroidism is associated with hypogonadotropic hypogonadism, which is reversible with thyroid hormone replacement therapy. The same has been seen in our study also that after levothyroxine replacement there was significant improvement in free testosterone level, significant improvement in ADAMS score, although predominance of hypogonadotropic hypogonadism was not that significant but still some degree of relevance was observed.

Source:

Abstract# 1038898: Effect of Levothyroxine Replacement Therapy on Testosterone, LH, FSH Levels in Men with Overt Hypothyrodism. Endocrine Practice. | VOLUME 27, ISSUE 6, SUPPLEMENT , S188, JUNE 01, 2021
 
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Testosterone replacement therapy: role of pituitary and thyroid in diagnosis and treatment

Crosstalk among hormones characterizes endocrine function, and assessment of the hypogonadal man should take that into consideration. In men for whom testosterone deficiency is a concern, initial evaluation should include a thorough history and physical exam in which other endocrinopathies are being considered. Hypogonadism can be associated with both pituitary and thyroid dysfunction, for which appropriate biochemical evaluation should be undertaken in certain clinical scenarios. If low serum testosterone is confirmed measurement of luteinizing and follicle stimulating hormones (LH and FSH respectively) is essential to establish whether the hypogonadism is primary or secondary. In secondary hypogonadism measurement of prolactin is always necessary, and measurement of other pituitary hormones, along with pituitary imaging, may be indicated. Checking thyroid function may also be enlightening, and can raise additional therapeutic considerations. Correction of other pituitary axes may attenuate the need for testosterone replacement therapy in some cases.

 
The Interrelationships Between Thyroid Dysfunction and Hypogonadism in Men and Boys

Thyroid hormone deficiency affects all tissues of the body, including multiple endocrine changes that alter growth hormone, corticotrophin, glucocorticoids, and gonadal function. Primary hypothyroidism is associated with hypogonadotropic hypogonadism, which is reversible with thyroid hormone replacement therapy. In male children follicle-stimulating hormone (FSH) is elevated and associated with testicular enlargement without virilization. Men with primary hypothyroidism have subnormal responses of luteinizing hormone (LH) to gonadotropin-releasing hormone (GnRH) administration and normal response to human chorionic gonadotropin (hCG). Free testosterone concentrations are reduced in men with primary hypothyroidism and thyroid hormone replacement normalizes free testosterone concentrations. In men with primary hypothyroidism, prolactin is not consistently elevated (except in men and children with longstanding severe primary hypothyroidism), but prolactin declines following thyroid hormone replacement therapy. Thyroid hormone is known to affect sex hormone-binding hormonal globulin (SHBG) concentrations. Men with hyperthyroidism have elevated concentrations of testosterone and SHBG. Thyroid hormone therapy in normal men may also duplicate this elevation. In addition estradiol elevations are observed in men with hyperthyroidism, and gynecomastia is common in them as well. In contrast to patients with primary hypothyroidism, men with hyperthyroidism exhibit hyperresponsiveness of LH to GnRH administration and subnormal responses to hCG. Radioactive iodine therapy (RAI) of men treated for thyroid cancer produces a dose-dependent impairment of spermatogenesis and elevation of FSH up to approximately 2 years. Permanent testicular germ cell damage may occur in men treated with high doses of RAI. RAI commonly increases serum concentrations of FSH and LH while reducing inhibin B levels without affecting serum concentrations of testosterone. Thus, radioiodine therapy transiently impairs both germinal and Leydig cell function that usually recover by 18 months posttherapy.
 
Effect of Adequate Thyroid Hormone Replacement on the Hypothalamo-Pituitary-Gonadal Axis in Premenopausal Women with Primary Hypothyroidism


Background: While the effects of thyroxine (T4) replacement on improving gonadal function in hypothyroid men has been well documented, the same has not been adequately studied in hypothyroid premenopausal women.

Methodology: Premenopausal women with overt hypothyroidism (thyroid-stimulating hormone [TSH] > 15 IU/L) were tested in the early follicular phase of their natural menstrual cycles or after a progesterone challenge for gonadotropins, estradiol (E2), and prolactin (PRL). They were then treated adequately with T4 replacement and retested under similar circumstances for the same parameters ≥2 months after the restoration of euthyroidism.

Results: Forty premenopausal hypothyroid women were evaluated at baseline and ≥2 months after adequate T4 replacement. At baseline, there was an inverse correlation of the gonadotropins (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and TSH, prolactin (PRL) and free T4 (fT4), and E2 and PRL. After normalization of the thyroid function, there was a significant fall in PRL (p < 0.001) accompanied by a rise in serum E2 (p < 0.001). There were no changes in the levels of the gonadotropins LH and FSH. The proportion of patients with hyperprolactinemia fell 5-fold, from 5/40 to 1/40. While there were 5 patients with low estrogen prior to treatment, there were none with hypoestrogenemia after treatment.

Conclusion: Hypothyroidism is associated with a reversible partial suppression of the hypothalamo-pituitary-gonadal axis in premenopausal women, demonstrated by lower E2 along with a mild elevation of PRL. Treatment of hypothyroidism improves the level of estrogen and lowers the level of PRL.

 
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