Disorders of sex hormones

Disorders of sex hormones are the disorders occurring due to problem in the areas endocrine system governing hormones related to reproductive system and the organs related to the same.

1. Disorders of Sex hormones By Drashti Patel Assistant Professor Department of Pharmacology L J University

2. Introduction Secretion of hormones responsible for maintaining sexual characters controlled by Brain. The sex hormones are a group of hormones responsible for controlling puberty, reproduction, birth and lactation . Sex hormone disorders/Reproductive hormone disorders are medical conditions that affect the different glands and organs of the body responsible for the production of the sex hormones. It is either an overproduction or underproduction of the hormones responsible for unusual sexual characteristics and development.

3. In females – Estrogen produced by ovaries. In males – testosterone produced by testicles. Testosterone are also produced by females, but if it is not in balance then women may experience symptoms including menstrual cycle irregularities, Hirsutism (extra hair growth), and acne. When males do not produce enough testosterone they may experience a decline in libido (sex drive), erectile dysfunction, loss of muscle and loss of body hair.

4. Classification of disorders Disorders of sex organ development Hermaphrodism – reproductive organs of both sex Congenital adrenal hyperplasia Gonadal dysgenesis Androgen insensitivity syndromes Hypogonadism ( Gonadotropin deficiency) Inherited Kallmann syndrome – delayed/absent puberty Klinefelter syndrome – XXY syndrome Turner syndrome – Female with only 1 ‘X’ chromosome Aquired Ovarian failure (pre-mature menopause) Testicular failure

5. Disorders of puberty Delayed puberty Precocious puberty Menstrual function fertility disorders Amenorrhoea Polycystic ovary syndrome

6. Disorders of sex development Most common - Congenital adrenal hyperplasia (CAH) CAH – results in females having genitals which look somewhat masculine Due to male hormones & Cortisol Another common - Androgen insensitivity syndromes Male does not respond to testosterone in usual way

7. Hypogonadism The sex glands, also called gonads, are primarily the  testes in men and the  ovaries in women. Diminished functional activity of gonads leads to hypogonadism  affects Spermatogenesis in male and Ovulation in Females Low androgen levels = Hypoandrogenism Low Estrogen levels = Hypoestrogenism

8. Types Primary : Testicles / Ovaries are affected LH/FSH like hormones are elevated Secondary : Problem in brain signaling i.e. Hypothalamus/ Pituitary LH/ FSH like Hormones levels are normal or low Based upon severity  may result in infertility

9. Primary Hypogonadism Mumps (Viral infection) are known to cause testicular failure A Varicocele can reduce hormonal production Enlargement of veins within the scrotum These defects are usually inherent within the gonads A few syndromes related to this type are : Klinefelter syndrome = 47 XXY genotype in male Turner syndrome = 45 X,0 in female

10. Secondary Hypogonadism It is also called as central Hypogonadism Examples of hypothalamic effects include : Kallmann syndrome Hypopituitarism Kallmann syndrome and PCOS are also called hypogonadotropic hypogonadism Hemochromatosis & Diabetes mellitus can cause secondary hypogonadism

11. Etiology Defective sexual development Premature menopause in adults

12. Complications Pre-mature loss of ovarian functions (below age of 40)  may result in Infertility Low estrogen  ovarian dysfunction  can cause hot flushes, night sweats, poor sleep and vaginal dryness Post menopausal period  Osteoporosis PCOS can lead to Irregular periods , loss of fertility, increased facial and abdominal hair, Tendency of insulin resistance showing symptoms of diabetes Male  low testosterone Osteoporosis and reduced strength and lower libido

13. Disorders of Puberty Delayed Puberty Precocious Puberty Delayed Puberty There are 2 cases in delayed puberty : Puberty delays a several years but still occurs normally later  Constitutional delay of growth Puberty delay may occur due to conditions like malnutrition, hypogonadism or body’s own delayed response to sex hormones  doesn’t occur in normal way

14. Etiology of delayed puberty: Following are the possible causes of delayed puberty. In females, prolonged high level of physical exertion as in case of athletes. Systemic diseases like celiac disease, inflammatory bowel disease, chronic renal failure. Under nutrition e.x . anorexia nervosa, zinc deficiency. Hypothalamic defects and diseases.

15. Gonadal defects and diseases. Absence or unresponsiveness of target organs Endocrine disorders like hypothyroidism, Cushing's syndrome. Cystic fibrosis. Different forms of congenital adrenal hyperplasia. Brain tumours.

16. Signs and Symptoms of delayed puberty : There are three types of effects due to pubertal delay. Lateness : There may be delay of two to three years or more. In girls, there is no breast development by 13 years . In boys, there is no testicular enlargement by 14 years or delay in development of genetalia by another 5 years. Discordance : In these cases, some aspects of physical development related to puberty are delayed and others are not eg . in most girls, the beginning stages of breast development precede pubic hair. In case of boys, pubic hair may grow but testes continue to be pre-pubertal in size. Specific disorders : Malnutrition or anorexia nervosa delay puberty. Poor growth may suggest possibility of celiac disease, hypopituarism or Turner syndrome . Reduced sense of smell ( hyposmia ) or no sense of smell ( anosmia ) suggests Kallmamm syndrome.

17. 2. Precocious Puberty In precocious puberty, it occurs at an unusually early age. The causes may be central or Peripheral . Central causes can be traced to hypothalamus or pituitary. In case of peripheral causes, they may be endogenous or exogenous. The causes are of two types : Central Peripheral

18. Central: The central causes are as follows: Damage to inhibitory system of brain due to infection, trauma or irradiation Langerhans cell histocytosis .

19. Peripheral: Secondary sexual development induced by sex steroid is one of the causes Symptoms include hypertension, hypotension, electrolyte abnormalities, ambiguous genetalia in females. Blood tests indicate high level of androgens with low level of cortisone. The causes are of 2 types : endogenous and exogenous Endogenous : Gonadal tumours Adrenal tumours Congenital adrenal hyperplasia Exogenous : Environmental exogenous hormones.

20. Signs and Symptoms of precocious puberty It includes development of the following before age 8 in girls and before age 9 in boys Signs and symptoms in girls Breast growth First period (menarche) Signs and symptoms in boys: Enlarged testicles and penis Facial hair Deepening voice Signs and symptoms in both boys and girls. Pubic or underarm hair Rapid growth Acne Adult body odour

21. Complication of precocious puberty Children with precocious puberty may grow quickly at first and be tall But since their bones mature more quickly than normal, they often stop growing earlier than usual. This can cause them to be shorter than average adults. Social and emotional problems: Girls and boys who begin puberty long before their peers may be extremely self conscious about the changes occurring in their bodies.

22. Menstrual Function or Fertility Disorders: There are two forms of fertility disorders related to menstrual function amenorrhea and polycystic ovary disease

23. Amenorrhea: Absence of a menstrual period in women of reproductive age. It is of two types: primary and secondary. In case of primary amenorrhea, there may be developmental problems like absence of uterus, failure of ovary to receive or maintain egg cells. In case of secondary amenorrhea, the cause may be hormonal disturbances from hypothalamus and pituitary

24. Causes of amenorrhea: Low Body Weight : Easy mobilization of energy is necessary to maintain regular menstrual cycles Thus the cause of amenorrhea is low energy availability. Drug Induced Amenorrhea : Oral contraceptives - Only progestogen or high dose oral contraceptives cause amenorrhea. Opiate like heroin, Antipsychotic drugs . Breast Feeding Physical : Amenorrhes can be caused by physical deformities. One example is MRKH syndrome in which Mullerian ducts do not develop, which prevent menstruation. Stress : Secondary amenorrhea

25. Complications Infertility Osteoporosis: It amenorrhoea is caused by low levels of estrogen then there is a risk of osteoporosis because estrogen is involved in transfer of calcium to the bone.

26. Polycystic ovary syndrome (PCOS) Polycystic ovaries develop when the ovaries are stimulated to produce excessive amounts of androgenic hormones like testosterone due to one of the following problems : Release of excessive LH by anterior pituitary gland. High levels of insulin in blood of women whose ovaries are sensitive to the stimulus. The cysts are actually immature follicles. The follicles have developed from primordial follicles, but their development is stopped due to disturbed ovarian function. Women with PCOS experience increased frequency of hypothalamic GnRH pulses, which in turn results in increased LH/FSH ratio. A majority of women with PCOS have insulin resistance and/or are obese.

27. Adipose tissue possesses aromatase . testosterone Aromatase estradiol Excess of adipose tissue in obese women create excess androgens as well as estrogens.

28. Signs and Symptoms of PCOS : Menstrual Disorders : PCOS produces oligomenorrhea or amenorrhea. Other types of menstrual disorders may occur. Infertility : It results directly from anovulation . High Levels of Masculinising Hormones: It is known as hyperandrogenism . Its most common signs are acne and hirsutism . It may produce hypermenorrhea and androgenic alopecia Metabolic Syndrome : There is a tendency towards central obesity and symptoms associated with insulin resistance. Serum insulin, insulin resistance and homocysteine levels are high in women with PCOS

29. Complications of PCOS Infertility : Every woman with PCOS may not be infertile. Those women who have anovulation may turn out to be infertile. Hirsutism and Acne : A Standard contraceptive pill is frequently effective in reducing hirsutism . Androgenic drug like Norgestrel and Livonorgestrel should be avoided due to their androgenic effects. Menstrual Irregularity : If fertility is not the primary aim, then menstruation can be regulated with a contraceptive pill.

30. Thank You

31. References Principles of pharmacology by HL Sharma and KK Sharma- 3 rd Edition, Paras Medical Publisher, 2019 Essentials of Medical pharmacology by KD Tripathi – 6 th Edition, JAYPEE, 2008 Pharmacology by Rang and Dale- 8 th Edition, Edinburgh: Churchill Livingstone, 2014