Female and Male Sex Hormones, Contraception, and HIV Study Guide

Key Receptors: The three central nuclear receptors are $Estrogen$ , $Progesterone$ , and $Androgen$ receptors.
Structural Features: * $Estradiol$ : Features an approximately $11\,\text{\AA}$ distance between its two alcoholic groups. * $Progesterone$ : Characterized by a $C=O$ at the $C3$ carbon and a stereochemical double bond $O$ at $C17$ .
Enhancing Bioavailability: The addition of a $[C \equiv C]$ (carbon triple bond) functional group increases the drug's bioavailability.
Androgen Activity Side Effects: Undesired in birth control; causes acne, hirsutism, voice changes, and breast tenderness.

Biosynthesis: Androgen production from cholesterol follows the adrenal pathway but specifically continues from androstenedione to $Testosterone$ ( $C19$ structure).
Metabolism of Testosterone: * $5\alpha\text{-reductase}$ : Converts testosterone to $Dihydrotestosterone$ ( $DHT$ ), the most potent male hormone, by adding a chiral hydrogen at $C4-C5$ . * $Aromatase$ ( $\text{Estrogen Synthase}$ ): Converts testosterone to $Estradiol$ using $O_2$ , $NADPH$ , and iron.
HPT Axis: System follows the pathway: $Hypothalamus \rightarrow GnRH \rightarrow Pituitary \rightarrow LH + FSH \rightarrow Testes$ .
Cellular Roles: * $Leydig Cells$ : Stimulated by $LH$ to produce testosterone. * $Sertoli Cells$ : Stimulated by $FSH$ to support spermatogenesis; produce $Androgen Binding Protein$ and $Inhibin B$ (negative feedback for $FSH$ ). * $Spermatogonia$ : Diploid stem cells that initiate spermatogenesis.
Pathologies: * $Gynecomastia$ : Enlarged male mammary tissue due to a decreased $Testosterone/Estrogen$ ratio. * $Androgenetic Alopecia$ : Pattern baldness involves hair follicle miniaturization triggered by $DHT$ . * $BPH$ ( $\text{Benign Prostate Hyperplasia}$ ): Prolonged $DHT$ exposure leads to urinary obstruction.

Hormonal Impacts: * $Estrogen$ : Builds the endometrial lining and triggers the $LH$ surge for ovulation. * $Progesterone$ : Stabilizes the lining for pregnancy; loss of both lead to menstruation.
Two-Cell Model of Synthesis: * $Theca Interna Cells$ : Express $CYP17A1$ to synthesize androgens from cholesterol. * $Granulosa Cells$ : Express $CYP19A1$ ( $\text{Aromatase}$ ) to convert theca-derived androgens into estrogens.
Fertilization: If occurs, the embryo produces $hCG$ ( $\text{human chorionic gonadotropin}$ ) to maintain the $Corpus Luteum$ and high progesterone levels.

Mechanism of Action (MOA): * $Estrogens$ : Suppress $FSH$ to inhibit development of the dominant follicle. * $Progestins$ : Suppress $LH$ secretion to inhibit ovulation.
Severe Risks (ACHES): Abdominal pain, Chest pain/ $SOB$ , Headaches (severe), Eye problems, Severe leg pain.
Combined Hormonal Contraception (CHC) Products: * Patch: Contains $Ethinyl Estradiol$ and $Norelgestromin$ or $Levonorgestrel$ ; less effective if weight > 198\,lb or BMI > 30\,kg/m^2. * Vaginal Rings: Includes $NuvaRing$ (refrigerated at pharmacy; $4$ -month shelf life at room temp) and $Annovera$ (reusable for $1$ year).
Progesterone-Only Pills (POPs): * $Norethindrone$ ( $0.35\,mg$ ): Requires strict adherence within a $3$ -hour window. * $Drospirenone$ ( $4\,mg$ ): Risk of hyperkalemia; offers more flexibility in dosing.
MN Pharmacist Protocol: Pharmacists may prescribe for those $18+$ or younger if a previous prescription exists ( < 3 years old).

Injectable (DMPA): $Depo-Provera$ given every $3$ months ( $104\,mg\,SQ$ or $150\,mg\,IM$ ). Black Box Warning for decreased $BMD$ ( $\text{Bone Mineral Density}$ ) if used > 2 years.
LARC (Long-Acting Reversible Contraception): * $IUDs$ : Copper ( $ParaGard$ up to $10$ years) or $Levonorgestrel$ ( $Mirena$ up to $8$ years). * $Implants$ : $Etonogestrel$ ( $68\,mg$ ) single rod; effective for $5$ years.
Emergency Contraception (EC): * $Levonorgestrel$ ( $OTC$ ): Effective within $72$ hours; efficacy drops if weight > 165\,lb. * $Ulipristal Acetate$ : Effective up to $5$ days; delays ovulation for $5$ days.

Infection Stages: * Acute Phase: $2-4$ weeks post-infection; flu-like symptoms and decline in $CD4+$ T cells. * Latent Phase: Low viremia; slow decline of $CD4+$ T cells over years. * AIDS: $CD4+$ count < 200/\mu L; emergence of opportunistic infections and neoplasms.
Medication Targets: Attachment/fusion, reverse transcription, integration, and protease maturation.
Opportunistic Pathogens: * Fungal/Protozoal: $Pneumocystis\,juroveci$ , $Toxoplasmosis$ , $Candidiasis$ . * Bacterial/Viral: $Mycobacterium\,avium\,complex$ , $Kaposi's\,sarcoma$ , $Cytomegalovirus$ .

Indications: Hypogonadism with serum testosterone levels confirmed below $12\,nmol/L$ or $350\,ng/dL$ .
Contraindications: Prostate/Breast cancer, hematocrit > 50\%, severe $OSA$ , or recent $MI/Stroke$ ( < 6 months).
Safety Monitoring: Verify hematocrit at baseline, at $3-6$ months, then annually.

Rectal Route: * Used for pediatric/geriatric or vomiting patients; reduces first-pass metabolism. * Physiology: Small volume ( $2-3\,mL$ ) of mucous fluid; requires high water solubility and high lipophilicity for absorption.
Vaginal Route: * Advantages: Avoids first-pass; continuous delivery via rings. * Physiology: Acidic $pH$ during child-bearing years; surface area increased by epithelial folds.