Male and Female Hormones

Selective estrogen receptor modulators (SERMs)

Activate estrogen receptors on select tissues - block effect of estrogen on other tissues Activate bone: increased bone strength, beneficial to lipids Block receptors on breast and uterine tissue - reduced cancer risk Drug: Raloxifine

Anti-androgens: common adverse effects and implications for physical therapy

Adverse effects: Erectile dysfunction, vasodilation, peripheral edema, headache, dizziness, MI and CVA, bone and joint pain Evaluation: assess vitals, assess peripheral edema, assess bone/joint pain Intervention: need to incorporate strength exercises to counter skeletal muscle loss secondary to less testosterone , take vitals, higher risk for falls, use caution with exercise due to risk for stroke and MI, use caution with activities that could promote vasodilation Education: report prolonged adverse effects to PCP

SERMs: common adverse effects and implications for physical therapy

Adverse effects: stroke, hot flashes, leg cramps, DVT Evaluation: be alert for signs of CVA, be alert for signs of DVT, assess leg cramps Intervention: use caution during exercise secondary to stroke risk , if able - use weight bearing exercises to benefit bone, measure vitals Education: signs of CVA, report prolonged adverse effects to PCP

Estrogen and Progesterone (Females)

Estrogen and progesterone promote sexual differentiation of the developing female fetus and female sexual maturation during puberty. The ovaries produce estrogen and progesterone. Estrogen promotes maturation of external genitalia, uterus, oviducts, and vagina - breast development, deposition of fat stores, and pelvic girdle widening. Progesterone is more important than estrogen in maintaining pregnancy.

Anti-androgens

Androgen inhibitor - useful in prostate cancer, especially in benign prostatic hyperplasia (one of the side effects that can occur with androgen therapy is prostate cancer/prostate cell growth) GnRH (gonadotropin releasing hormone) analog - seems counterintuitive, but it works: increase in GnRH will lead to an increase in LH and FSH secretion - initially, will increase LH production (and LH increases testosterone) - after some time, GnRH receptors become desensitized and down regulate the receptors to the analog GnRH antagonist: blocks GnRH receptor on the anterior pituitary and causes an immediate decrease in LH

Androgen Adverse Effects

Children: accelerated sexual maturation, premature closure of epiphyseal growth plates (growth in long bones is affected) Women: Hirsutism (facial hair), deepening of the voice, irregular period, acne Men: bladder irritation, breast swelling/soreness (gynecomastia), increased prostate cancer risk Both sexes: edema, hyperkalemia, mood changes Long term use: hepatic damage and carcinoma, hypertension, hyperlipidemia (HHH)

Clinical uses of testosterone

Conditions in which testosterone therapy is needed: removal of testicle(s), testicular failure, lack of LH production, aging (in men, andropause can occur after the age of 70 (may or may not occur), delayed puberty, catabolic states (testosterone is an anabolic steroid, so it can be used to build things back up) - chronic infections, severe trauma, severe burns, recovery from extensive surgery, HIV related muscle wasting

Estrogen and progesterone therapy

Estradiol (most active form of estrogen) and medroxyprogesterone Conditions: peri-menopausal symptoms (i.e. hot flashes), menopause, ovariectomy, hypogonadism, failure of ovary development, postmenopausal osteoporosis, may help decrease LDL levels and increase HDL levels, menstrual irregularities (amenorrhea, dysmenorrhea, functional uterine bleeding), endometriosis (uterine-like tissue growths in the pelvic cavity), carcinoma (metastatic male breast cancer and postmenopausal areas cancer, uterine cancer adjunctive therapy)

Adverse effects of estrogen and progesterone

Estrogen: MIST - MI, stroke, thromboembolism, increased ovarian and endometrial cancers Progesteron: PET U - pulmonary embolism, embolic stroke, thrombophlebitis, unpredictable uterine bleeding Estrogen and progesterone combined (in addition to the above adverse effects): sodium and water retention

Androgen use and implications for physical therapy

Evaluation/assessment: assess for hepatotoxicity, assess for edema, assess for mood changes Intervention: do not apply head over the area of androgen application (if transdermal - vasodilation would increase how fast the drug is absorbed), develop a resistance program to capitalize on the medication's effect if it is used for muscle wasting Education: report prolonged adverse effects to PCP, look for mood changes

Estrogen and progesterone use and implications for physical therapy

Evaluation/assessment: be alert for signs of MI/CVA, monitor signs of venous thrombosis, measure vitals, measure edema, higher risk for falls Intervention: higher risk for falls, measure vitals, use caution with exercise, avoid transdermal or topical site Education: signs of MI/CVA, tobacco use (tobacco plus estrogen/progesterone can increase risk for heart attack and stroke even more), report prolonged adverse effects to PCP

Follicular phase

FSH and LH are released from the anterior pituitary gland. FSH stimulates growth of about 20 eggs in a shell (follicle). FSH triggers an increase in estrogen. The rise in estrogen shuts off FSH release via negative feedback. Decrease in FSH prevents other eggs from developing. One follicle becomes dominant and suppresses all the other follicles in the group until they die. The dominant follicle releases estrogen and undergoes maturation and releases the egg. Estrogen causes thickening of the endometrium as well as an increase in vascularization (helps prepare the uterus to support a potential fertilized egg)

Pregnancy and Parturition Hormones (fertilized egg implants onto uterine wall)

Fertilization encourages continued production of progesterone. Human chorionic gonadotropin (hCG) is released from the fertilized ovum. hCG replaces LH. The corpus luteum continues to produce progesterone via hCG stimulation. After 9-14 weeks, the corpus luteum begins to degenerate and the placenta takes over steroid production. Progesterone release continues throughout pregnancy to maintain the uterus and placenta during pregnancy and prepares the mammary glands for lactation.

Contraceptives: adverse effects

Generally, well tolerated Adverse effects: MI (increased risk with smoking or advanced age > 35), nausea, abdominal cramping, headache, dizziness, depression, weight gain Evaluation: be alert for mood changes, be alert for signs of MI, periodically measure weight, higher risk for falls Intervention: higher risk for falls Education: signs of MI, changes to mood, report prolonged adverse effects to PCP Nutrition - in the first 8 weeks of pregnancy, the neural tube develops and closes - part of what helps that formation and closure if folic acid/folate - increased risk for spina bifida with deficiency in this nutrient For women who are sexually active, they need to be encouraged to take a folic acid supplement to ensure that there is adequate folic acid in the system if conception occurs so there is not a chance for neural tube defects • Most of the time, they are well tolerated

Termination

If the egg is not fertilized or iff implantation does not occur: The corpus luteum begins to regress due to lack of LH and FSH. The corpus luteum cannot produce adequate amounts of estrogen and progesterone to maintain the endometrium. The endometrium begins to slough off.

Menstrual Cycle

In non-pregnant, post-pubescent females, estrogen and progesterone exert their effects in a cyclic pattern: generally, a 28-day routine - follicular phase, ovulation, luteal phase, and termination stage

Contraceptives: mechanism of action

Inhibit ovulation: high levels of estrogen and progesterone inhibit the release of LH and FSH via negative feed back - inhibition of mid-cycle LH surge inhibits ovulation Impair development of endometrium: does not develop to the same extent as endogenous stimulation Increased cervical mucus: more difficult for sperm to fertilize the ovum

Sex hormones

Male hormones: testosterone Female hormones: estradiol (most potent form of estrogen) and progesterone The hypothalamus control the production of these hormones. Production occurs in the adrenal cortex as well as in the testes and ovaries.

Common Drug Formulations

Oxandrolone and stanozolol (both given orally) These drugs are not corticosteroids or beta blockers, respectively even though they have the characteristic suffixes.

Anatomy (males)

Sertoli cells line the seminiferous tubules - they are responsible for the development (spermatogenesis) and maturation of sperm. Leydig cells are located in the interstitial between the tubules and are responsible for creating testosterone. The seminiferous tubules lead to the epididymis.

Physiologic effects of testosterone

Testicular testosterone secretions begin at puberty - they induce secondary sex characteristics: spermatogenesis - testosterone enters the seminiferous tubules and stimulates sperm production in the Sertoli cells.

Ovulation - Near Day 14

The anterior pituitary gland secretes a large burst of LH and secretes a small burst of FSH as well. The LH surge causes follicle rupture and releases the ovum from the ovary. The ovum begins to travel toward the uterus via the Fallopian tube. After ovum release, the follicle fills with lipids and becomes a corpus luteum.

Luteal phase

The corpus luteum continues to grow and develop through about day 21. It secretes both estrogen and progesterone - increases thickness and vascularization of the endometrium. Progesterone causes the uterine glands to secrete mucus - creates a more favorable environment for egg implantation

Androgen source and regulation

The hypothalamus releases GnRH (gonadotropin releasing hormone), which regulates LH (luteinizing hormone) and FSH (follicle stimulating hormone). LH directly influences testosterone production in Leydig cells. FSH stimulates Sertoli cells which are responsible for the development and maturation of sperm. FSH stimulates androgen binding and protein production- because FSH and LH need to have a binding protein, FSH assists with this so they can travel through the blood. Androgen binding protein helps concentrate testosterone in the seminiferous tubules and helps testosterone reach the epididymis. A negative feedback system exists to control testosterone concentration - androgen production is not cyclic as it is in females.